Regulación por helmintos de las respuestas inmunitarias del hospedero / Helminth regulation of host immune responses

Introducción: durante las últimas dos décadas se ha producido una rápida acumulación de conocimientos sobre la inmunología de las helmintosis. La información ahora disponible permite un mejor entendimiento de los mecanismos defensivos del hombre contra la infección por helmintos. Otra área del saber sobre la inmunología de las helmintosis, la relacionada con la regulación de las respuestas inmunitarias del hospedero ejercida por el parásito, con sus muy disímiles implicaciones clínicas y epidemiológicas, también se ha beneficiado de la expansión cognoscitiva de los últimos años. Objetivos: revisar lo publicado sobre las evidencias, mecanismos y consecuencias de la regulación de las respuestas inmunitarias del hospedero ejercida por los helmintos. Métodos: con el auxilio de diferentes buscadores electrónicos, se realiza una revisión de los artículos sobre helmintos, helmintosis y regulación de las respuestas inmunitarias del hospedero publicados durante el período 1995-2015. Algunas monografías y artículos originales fechados con anterioridad al intervalo mencionado también fueron consultados. Resultados: se expone y analiza, y hasta donde es posible se sistematiza, la información colectada sobre los temas seleccionados. Conclusiones: datos epidemiológicos, clínicos y experimentales evidencian que los helmintos logran modular las respuestas inmunitarias de sus respectivos hospederos y con ello sobrevivir en aquellos. Adicionalmente, la modulación de las respuestas inmunitarias del hospedero tiene importantes consecuencias clínicas y epidemiológicas que, en aras de una práctica médica de mejor calidad, deben ser conocidas por los profesionales relacionados con el diagnóstico, tratamiento y control de estas parasitosis(AU)

Introduction: the last two decades have witnessed a swift accumulation of knowledge about the immunology of helminthiases. The information now available allows to better understand human defense mechanisms against helminth infection. Another area of knowledge about the immunology of helminthiases which has also benefited from such recent expansion of knowledge is the regulation of host immune responses by the parasite, with its great variety of clinical and epidemiological implications. Objectives: review publications about the evidence, mechanisms and consequences of the regulation of host immune responses by helminths. Methods: using various search engines, a review was conducted of papers about helminths, helminthiasis and regulation of host immune responses published from 1995 to 2015. Several monographs and original papers dated before that period were also consulted. Results: the information gathered about the topics selected is presented, analyzed and whenever possible systematized. Conclusions: epidemiological, clinical and experimental data show that helminths can modulate the immune responses of their hosts and thus survive within them. Additionally, modulation of host immune responses has important clinical and epidemiological consequences which should be known by professionals related to the diagnosis, treatment and control of these parasitic diseases in order to improve the quality of medical practice(AU)

Challenging Mycobacterium tuberculosi s dormancy mechanisms and their immunodiagnostic potential

ABSTRACT Mycobacterium tuberculosis is the etiologic agent of tuberculosis, one of the world's greatest cause of morbidity and mortality due to infectious disease. Many evolutionary mechanisms have contributed to its high level of adaptation as a host pathogen. Prior to become dormant, a group of about 50 genes related to metabolic changes are transcribed by the DosR regulon, one of the most complex and important systems of host-pathogen interaction. This genetic mechanism allows the mycobacteria to persist during long time periods, establishing the so-called latent infection. Even in the presence of a competent immune response, the host cannot eliminate the pathogen, only managing to keep it surrounded by an unfavorable microenvironment for its growth. However, conditions such as immunosuppression may reestablish optimal conditions for bacterial growth, culminating in the onset of active disease. The interactions between the pathogen and its host are still not completely elucidated. Nonetheless, many studies are being carried out in order to clarify this complex relationship, thus creating new possibilities for patient approach and laboratory screening.

New insights on the development of fungal vaccines: from immunity to recent challenges

Fungal infections are emerging as a major problem in part due to high mortality associated with systemic infections, especially in the case of immunocompromised patients. With the development of new treatments for diseases such as cancer and the acquired immune deficiency syndrome pandemic, the number of immunosuppressed patients has increased and, as a consequence, also the number of invasive fungal infections has increased. Several studies have proposed new strategies for the development of effective fungal vaccines. In addition, better understanding of how the immune system works against fungal pathogens has improved the further development of these new vaccination strategies. As a result, some fungal vaccines have advanced through clinical trials. However, there are still many challenges that prevent the clinical development of fungal vaccines that can efficiently immunise subjects at risk of developing invasive fungal infections. In this review, we will discuss these new vaccination strategies and the challenges that they present. In the future with proper investments, fungal vaccines may soon become a reality.

Mortality from Alzheimer's disease in Brazil, 2000-2009 / Enfermedad de Alzheimer: estudio de la mortalidad en Brasil, 2000-2009 / Doença de Alzheimer: estudo da mortalidade no Brasil, 2000-2009

Alzheimer's disease is the most prevalent type of dementia in the elderly worldwide. To evaluate the mortality trend from Alzheimer's disease in Brazil, a descriptive study was conducted with the Mortality Information System of the Brazilian Ministry of Health (2000-2009). Age and sex-standardized mortality rates were calculated in Brazil's state capitals, showing the percentage variation by exponential regression adjustment. The state capitals as a whole showed an annual growth in mortality rates in the 60 to 79 year age bracket of 8.4% in women and 7.7% in men. In the 80 and older age group, the increase was 15.5% in women and 14% in men. Meanwhile, the all-cause mortality rate declined in both elderly men and women. The increase in mortality from Alzheimer's disease occurred in the context of chronic diseases as a proxy for increasing prevalence of the disease in the population. The authors suggest healthcare strategies for individuals with chronic non-communicable diseases.

La enfermedad de Alzheimer es la demencia más frecuente entre adultos mayores en el mundo. Para evaluar la evolución de la mortalidad por la enfermedad de Alzheimer en Brasil, se ha desarrollado un estudio con datos del Sistema de Información sobre Mortalidad del Ministerio de Salud, durante el período 2000-2009. Se calcularon las tasas de mortalidad estandarizadas por edad y sexo en las capitales brasileñas y se registró la variación porcentual mediante ajuste de la regresión exponencial. El conjunto de las capitales presentó un aumento anual de las tasas de mortalidad en el grupo de edad de 60 a 79 años, de un 8,4% en mujeres y un 7,7% en hombres. En el grupo de 80 o más años, el aumento fue de un 15,5% en mujeres y un 14% en hombres. No obstante, hubo una disminución en la tasa de mortalidad por todas las causas entre los adultos mayores de ambos sexos. Se destaca un aumento de la mortalidad por enfermedad de Alzheimer en el contexto de las enfermedades crónicas como un proxy para la prevalencia de la enfermedad en la población, y se indican estrategias de asistencia en el cuidado de pacientes con enfermedades de larga duración.

A doença de Alzheimer é o tipo de demência que mais prevalece entre os idosos no mundo. Para avaliar a evolução da mortalidade por doença de Alzheimer no Brasil foi desenvolvido um estudo descritivo com os dados do Sistema de Informações sobre Mortalidade do Ministério da Saúde, no período de 2000 a 2009. Calcularam-se as taxas de mortalidade padronizadas por idade e sexo nas capitais brasileiras e se observou a variação percentual por meio de ajuste por regressão exponencial. Para o conjunto das capitais houve um crescimento anual nas taxas de mortalidade na faixa etária de 60 a 79 anos de 8,4% entre as mulheres e 7,7% entre os homens. No grupo etário de 80 anos e mais, o aumento foi de 15,5% entre as mulheres e 14% entre os homens. Contrariamente, verificou-se declínio da taxa de mortalidade por todas as causas entre os idosos em ambos os sexos. Destaca-se o aumento da mortalidade por doença de Alzheimer no contexto das doenças crônicas como um indicador aproximado da prevalência da doença na população, e são apontadas estratégias de assistência ao cuidado dos portadores de doenças de longa duração.

Presence of Toll Like Receptor-2 in spleen, lymph node and thymus of Swiss albino mice and its modulation by Staphylococcus aureus and bacterial lipopolysaccharide.

Toll-like receptors (TLR) are a family of pattern recognition receptors identifying pathogen associated molecular patterns (PAMPs). They play a critical role in the innate immune response during the initial interaction between the infecting microorganism and phagocytic cells. Here, we verified the presence of TLR-2 in spleen, lymph node and thymus of Swiss albino mice and their modulation after infection with Staphylococcus aureus and Lipopolysaccharide (LPS) challenge. It was seen that TLR-2 gene transcribed to its respective mRNA on S. aureus infection, in thymus, spleen and lymph node of mice but their levels and mode of expression varied. When challenged with LPS no prominent changes in the expression of TLR-2 receptor was observed but its expression increased gradually with time in the thymus, spleen and lymph node of S. aureus infected mice. TLR-2 expression was also found enhanced in infected splenic macrophages. By studying the serum cytokine profile the functionality of the receptor was measured. The results indicate the presence of TLR-2 in thymus, spleen and lymph node of Swiss albino strain of mice and that they are modulated by S. aureus.

Evaluation of ‘cattle’ and ‘Indian Bison’ type antigens of Mycobacterium avium subspecies paratuberculosis for diagnosis of Bovine Johne’s Disease using ‘indigenous ELISA’ and AGPT .

Two antigens (‘cattle’ type and ‘Indian Bison’ type) of Mycobacterium avium subspecies paratuberculosis were evaluated for diagnosis of Johne’s disease (JD) in a gaushala (cattle herd). Of the 160 cows of Sahiwal and Hariana breeds screened, 81 (50.6%) tested positive in ELISA and 66 (41.8%) in AGPT test. Using the two antigens, 33.5% tested positive in both the tests while 41.1% tested negative. Exclusively, only 8.2% tested positive in ELISA while 17.1% tested positive in AGPT. Two antigens together detected 58.9% prevalence of MAP in the gaushala. Individually, indigenous ELISA using antigen from native source of MAP proved superior to AGPT in the diagnosis of JD in cows.

Association among genetic predisposition, gut microbiota, and host immune response in the etiopathogenesis of inflammatory bowel disease

Inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC), is a chronic disorder that affects thousands of people around the world. These diseases are characterized by exacerbated uncontrolled intestinal inflammation that leads to poor quality of life in affected patients. Although the exact cause of IBD still remains unknown, compelling evidence suggests that the interplay among immune deregulation, environmental factors, and genetic polymorphisms contributes to the multifactorial nature of the disease. Therefore, in this review we present classical and novel findings regarding IBD etiopathogenesis. Considering the genetic causes of the diseases, alterations in about 100 genes or allelic variants, most of them in components of the immune system, have been related to IBD susceptibility. Dysbiosis of the intestinal microbiota also plays a role in the initiation or perpetuation of gut inflammation, which develops under altered or impaired immune responses. In this context, unbalanced innate and especially adaptive immunity has been considered one of the major contributing factors to IBD development, with the involvement of the Th1, Th2, and Th17 effector population in addition to impaired regulatory responses in CD or UC. Finally, an understanding of the interplay among pathogenic triggers of IBD will improve knowledge about the immunological mechanisms of gut inflammation, thus providing novel tools for IBD control.

Papel de los receptores tipo toll (TLRs) y receptores para dominios de oligomerización para la unión a nucleótidos (NLRs) en las infecciones virales / Role of toll-like receptors (TLRs) and nucleotide-binding oligomerization domain receptors (NLRs) in viral infections

Las células del sistema inmunitario (SI) son capaces de reconocer una gran variedad de microorganismos, a través de los receptores que se encuentran expresados y distribuidos a lo largo de su arquitectura celular. La interacción entre los patrones moleculares asociados a microorganismos o a daño (PMAM o PMAD) y los receptores reconocedores de patrones (RRP) presentes en las células del hospedero es un evento crítico que implica procesos intracelulares de señalización que finalizan en la expresión de mediadores tanto proinflamatorios como antivirales. Por consiguiente, de la integridad de estos receptores dependerá el buen funcionamiento de los distintos mecanismos de transducción de señal desde las membranas celulares al citoplasma y por ende, de la respuesta que el SI desencadene contra los patógenos entre ellos los agentes virales. De allí que, en esta revisión se discutirá el papel de los receptores tipo toll (TLRs) y receptores para dominios de oligomerización para la unión a nucleótidos (NLRs) en las infecciones virales, tomando como evidencia los estudios en humanos y ratones que a la fecha se conocen.

The immune system (IS) cells are capable of recognizing a wide variety of microorganisms, through receptors that are expressed and distributed throughout the cell architecture. The interaction between the pathogen-associated molecular patterns or damage-associated molecular patterns (PAMPs or DAMPs) and pattern recognition receptors (PRR), present in host cells, is a critical event that involves intracellular signaling processes that end up in the expression of both, proinflammatory and antiviral mediators. Accordingly, the proper functioning of the different mechanisms of signal transduction from the cell membrane to the cytoplasm will depend on the integrity of these receptors (PRR); and therefore, the IS response triggered against pathogens including viral agents. Hence, in this review we discuss the role of toll-like receptors (TLRs) and nucleotide-binding oligomerization domain receptors (NLRs) in viral infections, using as evidence the studies in humans and mice known to date.

Biología comparada del sistema de complemento en peces / Comparative biology of the complement system in fish / Biologia comparativa do sistema complemento em peixes

Dentro de la respuesta inmune humoral se encuentran componentes que mantienen la homeostasis de los organismos a través del control de agentes patógenos por medio de la opsonización, quimiotaxis de células fagocíticas facilitando el proceso de eliminación de lo extraño o sin su acompañamiento, en el caso de la formación de poros en la membrana celular. A un grupo de este conjunto de componentes de origen molecular proteico se denominósistema del complemento, el cual posee tres vías de activación (Clásica, Alternativa y Lectinas), funciona comoanafilatoxinas, reguladores y receptores. La presente revisión tiene como objetivo discutir acerca de los diferentes componentes del sistema del complemento en la escala animal enfocándose principalmente en peces teleósteos y mamíferos, como organismos modelos en busca de elucidar sus diferencias, homologías y respuestas.

Within the humoral immune response can be found components that maintain an organism’s homeostasis viacontrol of pathogenic agents using opsonization, chemotaxis of phagocytic cells which facilitates the processof elimination of foreign bodies, or in its absence, the formation of pores in the cellular membrane. One of these groups of components, of protein origin, is referred to as the complement system, which has 3 means of activation (Classic, Alternative, and Lectins) and functions as anaphylactic toxins, regulators and receptors. The aim of this review is to discuss the different components of the complement system in the animal kingdom, focusing principally on teleost fish and mammals, as model organisms in the search to elucidate their differences, homologies, and answers.

Dentro da resposta imune humoral encontram-se componentes que mantém a homeostase do organismo através docontrole de patógenos, por opsonização, quimiotaxia de células fagocíticas que facilita o processo de eliminaçãode corpos estranhos, ou na sua ausência, a formação de poros na membrana celular. Este conjunto de componentes moleculares de origem protéica são chamados de sistema complemento, que tem três vias de ativação (clássica, alternativa e lectinas), funciona como anafilatoxinas, reguladores e receptores. Esta revisão tem como objetivo discutir os vários componentes do sistema complemento na escala animal focando principalmente em peixes teleósteos e mamíferos como organismos modelos na busca de elucidar suas diferenças, homologias e respostas.

Phylogenetic analysis of Pneumocystis from pig lungs obtained from slaughterhouses in southern and midwestern regions of Brazil / Análise filogenética de Pneumocystis obtidos de pulmões de suínos provenientes de abatedouros da região sul e centro oeste do Brasil

The Pneumocystis genus is comprised of pathogens dwelling in the lungs of terrestrial, aerial, and aquatic mammals. Occasionally they induce severe pneumonitis, particularly in hosts with severe impairment of the immune system and progressively may fill pulmonary alveolar cavities causing respiratory failure. Molecular genetic studies revealed that Pneumocystis gene sequences present a marked divergence with the host species concerned. In the present study, the genetic diversity of Pneumocystis obtained from lungs of swines was examined by analyzing mitochondrial large subunit (mtLSU) and small subunit (mtSSU) rRNA sequences. The samples were obtained from two slaughterhouses located in two Brazilian states. Phylogenetic analysis demonstrated that genetic groupings within Pneumocystis organisms were in accordance with those of the corresponding hosts and that two clusters were formed. In conclusion, these data show that there are genetically distinct porcine Pneumocystis genotypes with at least two separate clusters in Brazil.

O gênero Pneumocystis compreende patógenos que residem em pulmões de animais terrestres, aéreos e aquáticos. Pode ocasionar uma grave pneumonia, particularmente em hospedeiros com o sistema imunológico seriamente comprometido, o que ocorre por meio de uma progressiva disseminação nas cavidades alveolares, causando insuficiência respiratória. Estudos genéticos, baseados em métodos moleculares, revelaram que as sequências dos genes de Pneumocystis apresentam marcante divergência de acordo com a espécie de hospedeiro. Neste estudo, a diversidade genética das amostras obtidas a partir de pulmões de suínos, provenientes de dois abatedouros localizados em dois estados brasileiros, foi examinada por análise das sequencias dos nucleotídeos dos produtos de PCR dos genes mtLSU e mtSSU do rRNA do Pneumocystis. O resultado confirma a tendência registrada em pesquisas com amostras de outros animais e permite concluir que existem, pelo menos, dois grupos filogenéticos distintos de Pneumocystis de suínos no Brasil.

Receptores tipo Toll, patogénesis y respuesta inmune a Helicobacter pylori / Toll-like receptors, pathogenesis and immune response to Helicobacter pylori

Helicobacter pylori coloniza el epitelio gástrico y la mayoría de las personas infectadas es asintomática, de 10 al 20 por ciento desarrolla gastritis atrófica, úlcera péptica, y menos de 3 por ciento genera cáncer gástrico. Estas patologías están determinadas por la relación entre los factores de virulencia de la bacteria y los factores del hospedero como predisposición genética y respuesta inmune. La inmunidad innata, representada principalmente por los receptores tipo Toll y tipo Nod, reconocen a sus ligandos específicos y activan factores de transcripción como NF-kB, AP-1, CREB-1, induciendo la producción de citocinas inflamatorias como IL-8, IL-12, IL-6, IL-1β, IL-18 y TNF-α, e IL-10. La inflamación crónica favorece los cambios de morfología gástrica, evita la apoptosis y favorece la angiogénesis, ocasionando lesiones neoplásicas y cáncer. El objetivo de esta revisión es analizar los mecanismos propuestos a la fecha de la respuesta inmune innata y adaptativa, involucrados en la infección por H. pylori, y se puntualiza en los mecanismos de eliminación o persistencia de la infección.

Helicobacter pylori colonize the gastric epithelial, most infected people are asymptomatic, 10 to 20 percent develop atrophic gastritis, peptic ulcer and less than 3 percent gastric cancer. These diseases are determined by the relationship between virulence factors of bacteria, host factors such as, genetic predisposition, and immune response. The innate immune response mainly represented by Toll-like receptors and Nod-like receptors that recognize their specific ligands, activate transcription factors as NF-kB, AP-1, CREB-1, inducing production of inflammatory cytokines such as IL -8, IL-12, IL-6, IL-1β, IL-18, TNF-α and IL-10. Chronic inflammation promotes gastric morphological changes, prevents apoptosis and allows angiogenesis generating neoplasic lesions and cancer. The aim of this review is to analyze the mechanisms proposed to date of the innate and adaptative immune response involved in H. pylori infection; remarking the mechanisms related in the elimination or persistence.

Porphyromonas gingivalis decreases osteoblast proliferation through IL-6-RANKL/OPG and MMP-9/TIMPs pathways.

Background: Porphyromonas gingivalis, an important periodontal pathogen, is closely associated with inflammatory alveolar bone resorption. This bacterium exerts its pathogenic effect indirectly through multiple virulence factors, such as lipopolysaccharides, fimbriae, and proteases. Another possible pathogenic path may be through a direct interaction with the host's soft and hard tissues (e.g., alveolar bone), which could lead to periodontitis. Aims and Objectives: The aim of the present study was to investigate the direct effect of live and heat-inactivated P gingivalis on bone resorption, using an in vitro osteoblast culture model. Results: Optical microscopy and 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide MTT assay revealed that live P gingivalis induced osteoblast detachment and reduced their proliferation. This effect was specific to live bacteria and was dependent on their concentration. Live P gingivalis increased IL-6 mRNA expression and protein production and downregulated RANKL and OPG mRNA expression. The effect of live P gingivalis on bone resorption was strengthened by an increase in MMP-9 expression and its activity. This increase was accompanied by an increase in TIMP-1 and TIMP-2 mRNA expression and protein production by osteoblasts infected with live P gingivalis. Conclusion: Overall, the results suggest that direct contact of P gingivalis with osteoblasts induces bone resorption through an inflammatory pathway that involves IL-6, RANKL/OPG, and MMP-9/TIMPs.