The Expression of Toll-like Receptors (TLR7 and TLR9) in Class III and Class IV of Recently Diagnosed Lupus Nephritis with 12-Month Follow-Up.

Renal involvement is an important cause of morbidity and mortality in systemic lupus erythematosus (SLE). The present study included patients with recently diagnosed Class III and Class IV lupus nephritis (LN) treated by Rheumatology who, upon the detection of alterations in their kidney function, were referred to Nephrology for the joint management of both medical specialties. The purpose of this study was to compare the plasma expression of Toll-Like Receptor 7 (TLR7) and TLR9 in healthy control (HC) subjects and newly diagnosed Class III and Class IV LN patients with 12-month follow-ups. The plasma expression of TLR7 and TLR9 proteins was determined by the ELISA method. A significant increase in the expression of TLR7 protein was found in Class III LN in the basal determination compared to the expression in the HC (p = 0.002) and at 12 months of follow-up (p = 0.03) vs. HC. The expression of TLR9 showed a behavior opposite to that of TLR7. TLR9 showed decreased protein expression in LN Class III patients' baseline and final measurements. The result was similar in the basal and final determinations of LN Class IV compared to the expression in HC. A significant decrease in SLEDAI -2K was observed at 12 months of follow-up in patients in Class III (p = 0.01) and Class IV (p = 0.0001) of LN. Complement C3 levels improved significantly at 12-month follow-up in Class IV patients (p = 0.0001). Complement C4 levels decreased significantly at 12-month follow-up in LN Class III compared to baseline (p = 0.01). Anti-DNA antibodies decreased significantly at 12 months of follow-up in Class IV LN (p = 0.01). A significant increase in proteinuria was found at 12 months of follow-up in Class III LN, compared to the baseline determination (p = 0.02). In LN Class IV, proteinuria decreased at 12 months of follow-up compared to baseline (p = 0.0001). Albuminuria decreased at 12 months of follow-up in LN Class IV (p = 0.006). Class IV LN, albuminuria also decreased at 12 months of follow-up (p = 0.009). Hematuria persisted in all patients and the glomerular filtration rate did not change. Three Class IV patients died before 12 months of follow-up from various causes. In conclusion, although the rheumatologic data appeared to improve, the renal function data remained inconsistent. Decreased expression of TLR9 and increased expression of TLR7 could be useful in the early diagnosis of Class III and Class IV LN is correct.

Evaluation of naturally acquired immune responses against novel pre-erythrocytic Plasmodium vivax proteins in a low endemic malaria population located in the Peruvian Amazon Basin.

BACKGROUND: Plasmodium vivax represents the most geographically widespread human malaria parasite affecting civilian and military populations in endemic areas. Targeting the pre-erythrocytic (PE) stage of the parasite life cycle is especially appealing for developing P. vivax vaccines as it would prevent disease and transmission. Here, naturally acquired immunity to a panel of P. vivax PE antigens was explored, which may facilitate vaccine development and lead to a better understanding of naturally acquired PE immunity. METHODS: Twelve P. vivax PE antigens orthologous to a panel of P. falciparum antigens previously identified as highly immunogenic in protected subjects after immunization with radiation attenuated sporozoites (RAS) were used for evaluation of humoral and cellular immunity by ELISA and IFN-γ ELISpot. Samples from P. vivax infected individuals (n = 76) from a low endemic malaria region in the Peruvian Amazon Basin were used. RESULTS: In those clinical samples, all PE antigens evaluated showed positive IgG antibody reactivity with a variable prevalence of 58-99% in recently P. vivax diagnosed patients. The magnitude of the IgG antibody response against PE antigens was lower compared with blood stage antigens MSP1 and DBP-II, although antibody levels persisted better for PE antigens (average decrease of 6% for PE antigens and 43% for MSP1, p < 0.05). Higher IgG antibodies was associated with one or more previous malaria episodes only for blood stage antigens (p < 0.001). High IgG responders across PE and blood stage antigens showed significantly lower parasitaemia compared to low IgG responders (median 1,921 vs 4,663 par/µl, p < 0.05). In a subgroup of volunteers (n = 17),positive IFN-γ T cell response by ELISPOT was observed in 35% vs 9-35% against blood stage MSP1 and PE antigens, respectively, but no correlation with IgG responses. CONCLUSIONS: These results demonstrate clear humoral and T cell responses against P. vivax PE antigens in individuals naturally infected with P. vivax. These data identify novel attractive PE antigens suitable for use in the potential development and selection of new malaria vaccine candidates which can be used as a part of malaria prevention strategies in civilian and military populations living in P. vivax endemic areas.

Epstein-Barr virus: the mastermind of immune chaos.

The Epstein-Barr virus (EBV) is a ubiquitous human pathogen linked to various diseases, including infectious mononucleosis and multiple types of cancer. To control and eliminate EBV, the host's immune system deploys its most potent defenses, including pattern recognition receptors, Natural Killer cells, CD8+ and CD4+ T cells, among others. The interaction between EBV and the human immune system is complex and multifaceted. EBV employs a variety of strategies to evade detection and elimination by both the innate and adaptive immune systems. This demonstrates EBV's mastery of navigating the complexities of the immunological landscape. Further investigation into these complex mechanisms is imperative to advance the development of enhanced therapeutic approaches with heightened efficacy. This review provides a comprehensive overview of various mechanisms known to date, employed by the EBV to elude the immune response, while establishing enduring latent infections or instigate its lytic replication.

Dynamics of Naturally Acquired Immunity Against Severe Acute Respiratory Syndrome Coronavirus 2 in Children and Adolescents.

OBJECTIVE: To evaluate the duration of protection against reinfection conferred by a previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children and adolescents. STUDY DESIGN: We applied 2 complementary approaches: a matched test-negative, case-control design and a retrospective cohort design. A total of 458 959 unvaccinated individuals aged 5-18 years were included. The analyses focused on the period July 1, 2021, to December 13, 2021, a period of Delta variant dominance in Israel. We evaluated 3 SARS-CoV-2-related outcomes: documented polymerase chain reaction-confirmed infection or reinfection, symptomatic infection or reinfection, and SARS-CoV-2-related hospitalization or death. RESULTS: Overall, children and adolescents who were previously infected acquired durable protection against reinfection with SARS-CoV-2 for at least 18 months. Importantly, no SARS-CoV-2-related deaths were recorded in either the SARS-CoV-2-naïve group or the previously infected group. The effectiveness of naturally acquired immunity against a recurrent infection reached 89.2% (95% CI, 84.7%-92.4%) at 3-6 months after the first infection and declined slightly to 82.5% (95% CI, 79.1%-85.3%) by 9-12 months after infection, with a slight nonsignificant waning trend seen up to 18 months after infection. Additionally, children aged 5-11 years exhibited no significant waning of naturally acquired protection throughout the outcome period, whereas waning protection in those aged 12-18 years was more prominent but still mild. CONCLUSIONS: Children and adolescents who were previously infected with SARS-CoV-2 remain protected to a high degree for 18 months. Further research is needed to examine naturally acquired immunity against Omicron and newer emerging variants.

Effect of regular physical exercise on human immunity / Efeitos da atividade física regular na imunidade humana / Efectos de la actividad física regular en la inmunidad humana

ABSTRACT Introduction: A suitable combination of physical exercise and nutrition can effectively improve the body's immunity and function. It has a positive effect and value on the healthy development of the body. Objective: To compare the immune function of athletes and non-athletes. We study the immune effect of spleen gland peptides on athletes. Methods: This study used different exercise methods, intensities, durations, and evaluated the effect of spleen peptide on the immune function of the body. Results: Physical exercise can improve human immunity. The spleen peptide directly exerts a positive two-way regulation effect on the immune function of athletes after intense and stressful exercise. Conclusion: The oral administration of spleen aminopeptidase enhances the athlete's body fluid and cellular immune function and effectively reduces the infection rate of the athlete's respiratory tract. Level of evidence II; Therapeutic studies - investigation of treatment results.

RESUMO Introdução: Uma associação adequada de atividade física e nutrição pode trazer melhorias efetivas à imunidade e à função corporais, com efeito positivo e custo-benefício no desenvolvimento saudável do corpo. Objetivo: Comparar a função imune de atletas e não-atletas. Estudamos o efeito imune de peptídeos do baço em atletas. Métodos: Este estudo utilizou atividade física em diferentes métodos, intensidades e duração, avaliando o efeito dos peptídeos do baço na função imune do corpo. Resultados: Exercícios físicos podem melhorar a imunidade humana. O peptídeo do baço tem um efeito regulador bidirecional no sistema imune de atletas depois de exercícios intensos ou com muita tensão. Conclusão: A administração oral de aminopeptidase esplênica aumenta os fluídos corporais e a função imune celular no corpo do atleta, efetivamente reduzindo os níveis de infecção de seu trato respiratório. Nível de evidência II; Estudos terapêuticos - investigação de resultados de tratamento.

RESUMEN Introducción: Una asociación adecuada de actividad física y nutrición puede ocasionar mejorías efectivas a la inmunidad y a la función corporales, con efecto positivo y costo-beneficio en el desarrollo saludable del cuerpo. Objetivo: Comparar la función inmunitaria de atletas y no atletas. Estudiamos el efecto inmunológico de los péptidos del bazo en atletas. Métodos: Este estudio utilizó actividad física en diferentes métodos, intensidades y duración, evaluando el efecto de los péptidos del bazo en la función inmune del cuerpo. Resultados: Ejercicios físicos pueden mejorar la inmunidad humana. El péptido del bazo tiene un efecto regulador bidireccional en el sistema inmunitario de atletas después de ejercicios intensos o de alto estrés. Conclusión: La administración oral de aminopeptidasa esplénica aumenta los fluidos corporales y la función inmunitaria celular en el cuerpo del atleta, reduciendo eficazmente los niveles de infección de sus vías respiratorias. Nivel de evidencia II; Estudios terapéuticos - investigación de resultados de tratamiento.

Paracoccidioidomycosis Protective Immunity.

Protective immunity against Paracoccidioides consists of a stepwise activation of numerous effector mechanisms that comprise many cellular and soluble components. At the initial phase of non-specific innate immunity, resistance against Paracoccidioides comes from phagocytic polymorphonuclear neutrophils, natural killer (NK) cells and monocytes, supplemented by soluble factors such as cytokines and complement system components. Invariant receptors (Toll-like receptors (TLRs), Dectins) which are present in cells of the immune system, detect patterns present in Paracoccidioides (but not in the host) informing the hosts cells that there is an infection in progress, and that the acquired immunity must be activated. The role of components involved in the innate immunity of paracoccidioidomycosis is herein presented. Humoral immunity, represented by specific antibodies which control the fungi in the blood and body fluids, and its role in paracoccidioidomycosis (which was previously considered controversial) is also discussed. The protective mechanisms (involving various components) of cellular immunity are also discussed, covering topics such as: lysis by activated macrophages and cytotoxic T lymphocytes, the participation of lytic products, and the role of cytokines secreted by T helper lymphocytes in increasing the efficiency of Paracoccidioides, lysis.

Rabies Vaccination of 6-Week-Old Puppies Born to Immunized Mothers: A Randomized Controlled Trial in a High-Mortality Population of Owned, Free-Roaming Dogs.

To achieve global elimination of human rabies from dogs by 2030, evidence-based strategies for effective dog vaccination are needed. Current guidelines recommend inclusion of dogs younger than 3 months in mass rabies vaccination campaigns, although available vaccines are only recommended for use by manufacturers in older dogs, ostensibly due to concerns over interference of maternally-acquired immunity with immune response to the vaccine. Adverse effects of vaccination in this age group of dogs have also not been adequately assessed under field conditions. In a single-site, owner-blinded, randomized, placebo-controlled trial in puppies born to mothers vaccinated within the previous 18 months in a high-mortality population of owned, free-roaming dogs in South Africa, we assessed immunogenicity and effect on survival to all causes of mortality of a single dose of rabies vaccine administered at 6 weeks of age. We found that puppies did not have appreciable levels of maternally-derived antibodies at 6 weeks of age (geometric mean titer 0.065 IU/mL, 95% CI 0.061-0.069; n = 346), and that 88% (95% CI 80.7-93.3) of puppies vaccinated at 6 weeks had titers ≥0.5 IU/mL 21 days later (n = 117). Although the average effect of vaccination on survival was not statistically significant (hazard ratio [HR] 1.35, 95% CI 0.83-2.18), this effect was modified by sex (p = 0.02), with the HR in females 3.09 (95% CI 1.24-7.69) and the HR in males 0.79 (95% CI 0.41-1.53). We speculate that this effect is related to the observed survival advantage that females had over males in the unvaccinated group (HR 0.27; 95% CI 0.11-0.70), with vaccination eroding this advantage through as-yet-unknown mechanisms.

Segurança e imunogenicidade da vacina trivalente inativada contra influenza durante a gravidez: uma revisão sistemática de estudos observacionais e randomizados

Seasonal influenza vaccination in pregnant women presents a unique challenge: it is known that influenza infection in pregnancy can cause severe morbidity, yet the benefits of maternal vaccination remain unclear. This study aims to conduct a systematic literature review synthesising available knowledge on the safety and immunogenicity of seasonal trivalent fragmented inactivated influenza (TIV) vaccine in pregnant women, and on the transmission and duration of maternal antibodies in the newborn. The search strategies were based on the defined acronym PICOS: (Participant) pregnant women; (Intervention) TIV vaccination; (Comparator) according to studies found in the review; (Outcomes) local and systemic adverse event/reaction, significant immunogenic improvement and maternally acquired immunity to influenza; (Study design) all types without restrictions. The following databases were searched: Web of Science (WoS), Medline (via PubMed), Embase, LILACS/VHL and CINAHL, from database inception until July 2018. Titles and abstracts were screened to identify potentially-relevant studies, which were then read in full. Data was extracted using a standardized form; the most relevant findings were summarized in a narrative synthesis. Methodological validity and quality will be assessed by standardized critical assessment tools, based on the Evaluation, Development and Rating Classification (GRADE) guidelines. The Electronic research found 133 articles at WoS, 1442 at Medline, 2157 at Embase, 1017 at LILACS/VHL and 391 at CINAHL. The selection of titles and abstracts resulted in 118 observational studies and 5 RCTs. After the examination of the full texts, 21 articles were excluded because they did not include the full scope of the study. The observational studies (97) included 41 cross-sectional studies and 3 case controls. Eight studies reported local and systemic adverse events. The most reported events in pregnant women were: Local pain, skin eruption, muscle pain, fever, malaise and headache. In newborns: Meningitis, Low weight, Influenza like and Fetal death. Regarding immunogenicity data, they showed that pregnant women have the ability to produce rates within or above the recommended standard. According to the survey of data and reports from the studies analyzed, it is possible to say that the inactivated trivalent vaccine against influenza is beneficial for pregnant women.

A vacinação sazonal da influenza em gestantes apresenta um desafio único: sabe-se que a infecção da influenza na gravidez pode causar uma morbidade grave, mas os benefícios da vacinação materna permanecem pouco claros. Este estudo visa conduzir uma revisão sistemática da literatura, sintetizando o conhecimento disponível sobre a segurança e imunogenicidade da vacina da influenza sazonal trivalente fragmentada inativada (TIV) em gestantes, e sobre a transmissão e duração dos anticorpos maternos no recém-nascido. As estratégias de busca foram baseadas na sigla definida PICOS: (Participante) mulheres grávidas; (Intervenção) vacinação TIV; (Comparador) de acordo com estudos encontrados na revisão; (Resultados) evento/reação adversa local e sistêmica, melhora imunogênica significativa e imunidade materna à influenza; (Desenho do estudo) todos os tipos sem restrições. As seguintes bases de dados foram pesquisadas: Web of Science (WoS), Medline (via PubMed), Embase, LILACS/VHL e CINAHL, desde o início da base de dados até julho de 2018. Títulos e resumos foram selecionados para identificar estudos potencialmente relevantes, os quais foram então lidos na íntegra. Os dados foram extraídos utilizando um formulário padronizado; os achados mais relevantes foram resumidos em uma síntese narrativa. A validade metodológica e a qualidade serão avaliadas por ferramentas padronizadas de avaliação crítica, com base nas diretrizes de Avaliação, Desenvolvimento e Classificação de Classificação (GRADE). A pesquisa eletrônica encontrou 133 artigos na WoS, 1442 no Medline, 2157 no Embase, 1017 na LILACS/VHL e 391 na CINAHL. A triagem dos títulos e resumos resultou em 118 estudos observacionais e 5 RCTs. Após o exame dos textos completos, 21 artigos foram excluídos por não contemplarem o escopo completo do estudo. Os estudos observacionais (97) incluíram 41 estudos transversais e 3 casos- controles. Oito estudos relataram eventos adversos locais e sistêmicos. Os eventos mais relatados em gestantes foram: Dor local, Erupção cutânea, Dor muscular, Febre, Mal-estar e Cefaleia. Nos recém-nascidos foram: Meningite, Baixo peso, Influenza like e Morte fetal. Em relação aos dados de imunogenicidade demonstraram que mulheres gravidas possuem a capacidade de produzir taxas dentro ou superior ao padrão recomendado. Conforme o levantamento de dados e relatos dos estudos analisados é possível dizer que a vacina trivalente inativada contra a influenza é benéfica para gestantes.

The Effect of a Competitive Futsal Match on T Lymphocyte Surface Receptor Signaling and Functions.

In this study, the lymphocyte activation status (surface expression of CD95, CD28, CD25, and CTLA-4), lymphocyte number, lymphocyte subpopulations, lymphocyte necrosis and/or apoptosis, and lymphocyte release of reactive oxygen species (ROS) were investigated in blood samples from 16 futsal athletes before and immediately following a competitive match. Lymphocytes were isolated from the blood samples, and the cellular parameters were assessed by flow cytometry. The futsal match induced lymphocytosis and lymphocyte apoptosis, as indicated by phosphatidylserine externalization, CD95 expression, and DNA fragmentation. Additionally, the competitive match induced the necrotic death of lymphocytes. No differences in the percentage of CD4+ and CD8+ T cells or in the T-helper/suppressor profile between before and immediately after the match were observed. Additionally, after the futsal match, the CD95 and CD28 expression levels were decreased, and the lymphocytes spontaneously released higher levels of ROS. Regardless of the origin, the situation-specific knowledge of lymphocyte behavior obtained herein may facilitate the design of strategies to control the processes that result in infection and tissue injury and that subsequently decrease athletic performance.

Placental and colostral transfer of antibodies reactive with enteropathogenic Escherichia coli intimins α, ß, or γ / Transferência placentária e colostral de anticorpos reativos a Escherichia coli enteropatogênica com expressão das intiminas α, ß, or γ

Abstract Objective: Intimins are protein adhesins of enteropathogenic Escherichia coli and enterohemorrhagic E. coli capable of inducing attachment and effacement lesions in enterocytes. Anti-intimin antibodies are important for the protection from enteropathogenic E. coli and enterohemorrhagic E. coli infections because these antibodies inhibit bacterial adhesion and impair the initial step of the pathogenesis. We studied the transfer of maternal anti-intimin antibodies from healthy Brazilian mothers to their newborns through the placenta and colostrum. Methods: Serum immunoglobulin G and secretory immunoglobulin A antibodies against conserved and variable regions of intimins α, β, and γ were analyzed using an enzyme linked-immunosorbent assay in the blood and colostrum from 45 healthy women as well as cord blood serum samples from their newborns. Results: The concentrations of antibodies reactive with α intimin were significantly lower than those of anti-γ and anti-conserved intimin antibodies in the colostrum samples. IgG serum antibodies reactive with all the subtypes of intimins were transferred to the newborns, but the concentrations of anti-conserved intimin serum antibodies were significantly higher in mothers and newborns than concentrations of antibodies against variable regions. The patterns of IgG transfer from mothers to newborns were similar for all anti-intimin antibodies. These values are similar to the percentage transference of total IgG. Conclusions: Anti-intimin antibodies are transferred from mothers to newborns through the placenta, and reinforce the protection provided by breastfeeding against diarrheagenic E. coli infections.

Resumo Objetivo: As intiminas são adesinas proteicas de Escherichia coli enteropatogênicas (EPEC) e enterro-hemorrágicas (EHEC) capazes de induzir as lesões attaching and effacing nos enterócitos. Anticorpos anti-intiminas são importantes para a proteção contra infecções por EPEC e EHEC porque esses anticorpos inibem a adesão bacteriana e impedem o passo inicial do mecanismo patogênico dessas bactérias. Nós estudamos a transferência de anticorpos maternos anti-intiminas de mães brasileiras saudáveis para os seus recém-nascidos através da placenta e do colostro. Métodos: Anticorpos séricos da classe IgG e secretórios da classe IgA (SIgA) reativos com as porções conservada (cons) e variáveis das intiminas α (vα), β (vβ) e γ (vγ) foram analisados pelo teste de ELISA no sangue e no colostro de 45 parturientes saudáveis e no sangue de cordão umbilical dos seus respectivos recém-nascidos. Resultados: As concentrações de anticorpos reativos com intimina vα foram significativamente mais baixas que as dos anticorpos anti-vγ e anti-cons nas amostras de colostro. Anticorpos IgG séricos reativos com todas as intiminas foram transferidos para os recém-nascidos, mas as concentrações de anti-cons foram significativamente mais altas tanto nas mães como nos recém-nascidos do que os anticorpos reativos com as regiões variáveis das intiminas. O padrão de transferência de IgG das mães para os recém-nascidos foi muito semelhante para todos os anticorpos anti-intiminas. Os valores de porcentagem de transferência foram semelhantes à transferência de IgG total. Conclusões: Anticorpos anti-intimina são transferidos das mães para os recém-nascidos pela placenta e corroboram a proteção contra infecções por Escherichia coli diarreiogênicas (DEC) conferida pelo aleitamento materno.

Placental and colostral transfer of antibodies reactive with enteropathogenic Escherichia coli intimins α, ß, or γ.

OBJECTIVE: Intimins are protein adhesins of enteropathogenic Escherichia coli and enterohemorrhagic E. coli capable of inducing attachment and effacement lesions in enterocytes. Anti-intimin antibodies are important for the protection from enteropathogenic E. coli and enterohemorrhagic E. coli infections because these antibodies inhibit bacterial adhesion and impair the initial step of the pathogenesis. We studied the transfer of maternal anti-intimin antibodies from healthy Brazilian mothers to their newborns through the placenta and colostrum. METHODS: Serum immunoglobulin G and secretory immunoglobulin A antibodies against conserved and variable regions of intimins α, ß, and γ were analyzed using an enzyme linked-immunosorbent assay in the blood and colostrum from 45 healthy women as well as cord blood serum samples from their newborns. RESULTS: The concentrations of antibodies reactive with α intimin were significantly lower than those of anti-γ and anti-conserved intimin antibodies in the colostrum samples. IgG serum antibodies reactive with all the subtypes of intimins were transferred to the newborns, but the concentrations of anti-conserved intimin serum antibodies were significantly higher in mothers and newborns than concentrations of antibodies against variable regions. The patterns of IgG transfer from mothers to newborns were similar for all anti-intimin antibodies. These values are similar to the percentage transference of total IgG. CONCLUSIONS: Anti-intimin antibodies are transferred from mothers to newborns through the placenta, and reinforce the protection provided by breastfeeding against diarrheagenic E. coli infections.

IgY pharmacokinetics in rabbits: implications for IgY use as antivenoms.

This paper presents the first study of chicken IgY pharmacokinetics (PK) in rabbits. We measured IgY blood serum concentrations using a specific high sensitivity ELISA method. The fast initial component observed when studying horse Fab, F(ab')2 or IgG was absent from IgY PK. During the first 80 min of observation there was only a single slow exponential decay, which sped up afterward to the point that IgY became undetectable after 216 h of observation; due to this time course, PK parameters were determined with trapezoidal integration. The most significant IgY pharmacokinetic parameters determined were (all presented as medians and their 95% confidence interval): Area Under the Curve = 183.8 (135.2, 221.5) mg·h·L(-1); Distribution volume of the central compartment·[Body Weight (BW)](-1) = 46.0 (21.7, 70.3) mL·kg(-1); Distribution volume in steady state·BW(-1) = 56.8 (44.4, 68.5) mLkg(-1); Mean Residence Time = 40.1 (33.6, 48.5) h; Total plasma clearance·BW(-1) = 1.44 (1.15, 1.66) mL·h(-1)·kg(-1). Anti IgY IgG titers determined by ELISA increased steadily after 72 h, and reached 2560 (1920, 5760) dilution(-1) at 264 h; anti-chicken IgG concentrations rose up to 3.19 (2.31, 6.17) µg/mL in 264 h. Our results show that IgY PK lacks the fast initial decay observed in other PK studies using horse IgG, F(ab')2 or Fab, remains in the body 39.0 (28.7, 47.2) % much as IgG and is ≈3 times more immunogenic that horse IgG in rabbits.

Modulation of cell proliferation, survival and gene expression by RAGE and TLR signaling in cells of the innate and adaptive immune response: role of p38 MAPK and NF-KB

Objective: The aim of this study was to evaluate a possible synergism between AGE-RAGE and TLR4 signaling and the role of p38 MAPK and NF-kB signaling pathways on the modulation of the expression of inflammatory cytokines and proliferation of cells from the innate and adaptive immune response. Material and Methods: T lymphocyte (JM) and monocyte (U937) cell lines were stimulated with LPS and AGE-BSA independently and associated, both in the presence and absence of p38 MAPK and NF-kB inhibitors. Proliferation was assessed by direct counting and viability was assessed by a biochemical assay of mitochondrial function. Cytokine gene expression for RAGe, CCL3, CCR5, IL-6 and TNF-α was studied by RT-PCR and RT-qPCR. Results: RAGE mRNA expression was detected in both cell lines. LPS and AGE-BSA did not influence cell proliferation and viability of either cell line up to 72 hours. LPS and LPS associated with AGE induced expression of IL-6 and TNF-α in monocytes and T cells, respectively. Conclusions: There is no synergistic effect between RAGE and TLR signaling on the expression of IL-6, TNF-α , RAGE, CCR5 and CCL3 by monocytes and lymphocytes. Activation of RAGE associated or not with TLR signaling also had no effect on cell proliferation and survival of these cell types. .

Production of anti-horse antibodies induced by IgG, F(ab')2 and Fab applied repeatedly to rabbits. Effect on antivenom pharmacokinetics.

We separated whole IgG, Fab and F(ab')2 fragments from horse plasma. We previously studied the pharmacokinetics of these immunoglobulins and fragments in rabbits and shown that Fab and F(ab')2 pharmacokinetics were well described by a three-exponential kinetics, while IgG and IgG(T) pharmacokinetics, however, deviated from the three-exponential kinetics 120 h after injecting a bolus of the immunotherapeutics; this departure was shown to be due to a surge of anti-horse antibodies occurring after 120 h, peaking at ≈260 h and decaying slowly afterward (Vázquez et al., 2010). We now describe antivenom pharmacokinetics and anti-horse IgG production in rabbits receiving three boluses (300 µg/kg, I.V.) of Fab, F(ab')2 or IgG separated by 21 days.

Mecanismos de modulación de la respuesta inmune por Chlamydia trachomatis asociados a infertilidad / Immune response modulation mechanisms induced by Chlamydia trachomatis associated with infertility

Introducción: la infertilidad, problema clínico y social que afecta del 13 al 15% de las parejas en el mundo, es causada, entre otros, por la enfermedad pélvica inflamatoria ocasionada por varios agentes infecciosos entre los cuales se destaca la Chlamydia trachomatis. Este agente infeccioso posee mecanismos moleculares con los cuales modula la respuesta inmune del huésped y produce cambios en la célula infectada para permitir su supervivencia, ocasionando que la respuesta del sistema inmunológico se establezca en forma crónica, con la consecuente inflamación permanente y con ello secuelas como cicatrices y obstrucción de la trompa de Falopio. El objetivo de esta revisión es ofrecer una actualización de conocimiento en inmunobiología de la infección por Chlamydia trachomatis y su relación con la infertilidad.Materiales y métodos: se realizó una revisión de la literatura en diferentes bases de datos: PubMed/ Medline, Science Direct, Ovid, desde enero del año 1995 a enero del 2012, incluyendo artículos de revisión y estudios clínicos.Resultados: en la actualidad se sostiene que la inmunomodulación que caracteriza la infección por Chlamydia trachomatis, los mediadores inflamatorios implicados en la respuesta inmune, y la posible aunque poco estudiada susceptibilidad genética del huésped, se relacionan estrechamente con la génesis de la infertilidad por factor tubárico.Conclusión: la infertilidad causada por Chlamydia trachomatis tiene su origen en la respuesta inmunológica del huésped y en la modulación por parte de este agente infeccioso, lo que lleva a inflamación crónica, cicatrización y obstrucción de la trompa de Falopio.

Introduction: Infertility is a clinical and social problem affecting 13% to 15% of couples around the world. One of its causes is the pelvic inflammatory disease, induced by several infectious agents, Chlamydia trachomatis standing out amongst them. This infectious agent has molecular mechanisms modulating the host immune response and producing changes in the infected cell to allow it to survive, casing a chronic immunological system response, with consequent permanent inflammation and sequelae such as cicatrices and obstruction of the fallopian tubes. This review was aimed at updating knowledge regarding the immune-biology of infection caused by Chlamydia trachomatis and its relationship with infertility. Materials and methods: A literature review was made using PubMed/MEDLINE, Science Direct and Ovid databases from January 1995 to January 2012, including review articles and clinical studies. Results: It is currently held that immunomodulation characterizing infection caused by Chlamydia trachomatis, the inflammatory mediators implicated in the immune response and possible (though little studied) host genetic susceptibility are closely related to the genesis of tubal infertility.Conclusion: Infertility caused by Chlamydia trachomatis has its origin in a host’s immunological response and this infections agent’s modulation leading to chronic inflammation, healing and obstruction of the fallopian tubes.

Modulação da proliferação, morte celular e expressão gênica de mediadores inflamatórios pela ativação de RAGE e TLR4 em células da resposta imune inata e adaptativa: papel das vias de sinalização p38 MAPK e NF-kB / Modulation of cell proliferation, survival and gene expression of inflammatory mediators by RAGE and TLR signaling in cells of the innate and adaptive immune response: role of p38 MAPK and NF-KB

O diabetes está associado à maior susceptibilidade à infecções e sepsis, demonstrando uma influência desta condição sobre a resposta imune. A doença periodontal é um tipo de infecção crônica, modulada pela resposta imune que apresenta maior prevalência e severidade em pacientes diabéticos. Nosso objetivo foi avaliar um possível sinergismo entre os receptores RAGE e TLR4 na modulação da proliferação celular, atividade metabólica, apoptose e expressão de citocinas inflamatórias em células da resposta imune inata e adaptativa. Como objetivo secundário, avaliamos o papel das vias de sinalização p38 MAPK e NF-kB na expressão dos genes inflamatórios por estas células após estimulação de RAGE e TLR4. Linhagens de células humanas de linfócitos T (JM) e monócitos (U937) foram estimulados com LPS e AGE-BSA tanto de forma independente como associados. A estimulação foi realizada também na presença e na ausência de inibidores bioquímicos para p38 MAPK (SB203580) e NF-kB (Bay 11-7082). A proliferação celular foi determinada por ensaio de exclusão azul de trypan, a apoptose pela via intrínseca e atividade metabólica foi avaliada por um ensaio bioquímico da função mitocondrial, a expressão de citocinas foi estudada por RT-PCR e RTqPCR e a ativação das vias de sinalização de interesse pelos estímulos utilizados foi investigada através de Western blotting. LPS e AGE-BSA não influenciaram a proliferação e sobrevivência celular de monócitos e linfócitos T após 24, 48 e 72 h. LPS, isoladamente ou associado a AGE, induziu a expressão de IL-6 e TNF-α em monócitos e células T, respectivamente. A ativação de p38 MAPK, mas não de NF-kB, foi necessária para a indução por LPS e LPS/AGE de IL-6 e TNF-α por LPS, isolado ou associado a AGE. A expressão de RNAm de RAGE foi detectada em ambos os tipos de célulares. RNAm de CCL3 foi expresso de forma mais marcante em monócitos, particularmente após estimulação com LPS. Não houve sinergismo na sinalização entre RAGE e TLR4 na modulação da expressão de IL-6, TNF-α, RAGE, CCR5 e CCL3 por monócitos e células T

Diabetes is associated to increased susceptibility to infections and sepsis, indicating that this condition modulates the immune response. Periodontal disease is one type of chronic infection, which is modulated by the immune response and presents with increased prevalence and severity in diabetic patients. Our objective was to evaluate a possible synergism between RAGE and TLR4 signaling on the modulation of cell proliferation, metabolic activity, apoptosis and gene expression of inflammatory cytokines by cells of the innate and adaptive immune response. As a secondary objective, we assessed the role of p38 MAPK and NF-kB signaling pathways on the expression of the inflammatory genes by these cells after stimulation of RAGE and TLR4. Human cell lines of T lymphocytes (JM) and monocytes (U937) were stimulated with LPS and AGE-BSA both independently and associated. Stimulation was also performed in the presence and absence of biochemical inhibitors for p38 MAPK (SB203580) and NF-kB (Bay 11-7082). Cell proliferation was determined by trypan blue dye exclusion assay, apoptosis by the intrinsic pathway and metabolic activity were assessed by a biochemical assay of the mitochondrial function, cytokine gene expression was studied by RTPCR and RT-qPCR and the activation of the selected signaling pathways after RAGE and TLR4 activation was investigated by Western blotting. LPS and AGE-BSA did not influence cell proliferation and survival 24, 48 and 72 h after stimulation. LPS, alone or associated with AGE-BSA, induced expression of IL-6 and TNF- mRNA by monocytes and T cells, respectively. Activation of p38 MAPK, but not of NF-kB, was required for LPS and LPS/AGE-induced induction of IL-6 and TNF. RAGE mRNA expression was detected in both cell types. CCL3 mRNA expression levels were higher in monocytes upon stimulation with LPS. There was no synergism between RAGE and TLR4 signaling on the expression of IL-6, TNF-, RAGE, CCR5 and CCL3 by monocytes and T cells

The role of MHC haplotypes H2d/H2b in mouse resistance/susceptibility to cyst formation is influenced by the lineage of infective Toxoplasma gondii strain

Toxoplasma gondii strains displaying the Type I/III genotype are associated with acquired ocular toxoplasmosis in humans. Here, we used a mice model to characterize some immunological mechanisms involved in host resistance to infection with such strains. We have chosen the Type I/III strains D8, G2 and P-Br, which cause a chronic infection in mice that resembles human toxoplamosis. Mice deficient of molecules MyD88, IFN-gamma, and IL-12 were susceptible to all three parasite strains. This finding indicates the importance of innate mechanisms in controlling infection. On the other hand, MHC haplotype did not influenced resistance/susceptibility; since mice lineages displaying a same genetic background but different MHC haplotypes (H2b or H2d) developed similar mortality and cyst numbers after infection with those strains. In contrast, the C57BL/6 genetic background, and not MHC haplotype, was critical for development of intestinal inflammation caused by any of the studied strains. Finally, regarding effector mechanisms, weobserved that B and CD8+ T lymphocytes controlled survival,whereas the inducible nitric oxide synthase influenced cyst numbers in brains of mice infected with Type I/III strains. These findings are relevant to further understanding of the immunologic mechanisms involved in host protection and pathogenesis during infection with T. gondii.

Cepas de Toxoplasma gondii que apresentam o genótipo I/III são associadas a toxoplasmose ocular adquirida em humanos. No presente trabalho, nós utilizamos um modelo da doença em camundongos para caracterizar mecanismos imunológicos envolvidos na resistência do hospedeiro à infecção por aquelas cepas. Escolhemos as cepas D8, G2 e P-Br, que causam infecção crônica em camundongos, semelhante à toxoplasmose humana. Camundongos deficientes em MyD88, IFN-G e IL-12 foram susceptíveis a infecções com todas as três linhagens do parasita. Esses dados indicam a importância de mecanismos inatos no controle da infecção. Por outro lado, o haplótipo do MHC não influenciou na resistência/susceptibilidade, na medida em que linhagens de camundongos com um mesmo "background'' genético, mas diferentes haplótipos de MHC (H2b e H2d) apresentam o índice de mortalidade e número de cistos semelhantes após a infecção com aquelas cepas do parasita. Em contraste, o "background'' genético de C57BL/6, mas não o haplótipo de MHC, foi crítico para o desenvolvimento de inflamação intestinal causada pelas cepas estudadas. Finalmente, com relação aos mecanismos efetores, observamos que linfócitos B e T CD8+ controlam a sobrevivência após infecção. Por outro lado, a ativação da enzima óxido nítrico sintase induzida foi um fator importante para controle do número de cistos cerebrais em camundongos infectados com cepas do Tipo I/III. Esses achados são relevantes para o melhor entendimento dos mecanismos imunológicos envolvidos na proteção e patogênese durante infecção com T. gondii.