Progress of research on immune escape mechanism of coronavirus / 中国药科大学学报

@#Coronavirus is an important pathogen of humans and animals. Among them, the novel coronavirus disease (COVID-19) breaking out in 2019 has brought a fatal threat to human health. The host"s innate immune response is the host"s first line of defense against pathogen invasion, but an excessive immune response can also aggravate viral infection and pathological damage. The immune escape of coronavirus is a critical pathogenic mechanism causing death. This work mainly reviews the pathogenic mechanism of coronavirus immune escape from several aspects such as host immunosensor, interferon, cytokine and coronavirus antagonizing host immune response, which provide a theoretical reference for the development of anti-coronavirus drugs.

The function and regulation of TET2 in innate immunity and inflammation

TET2, a member of ten-eleven translocation (TET) family as α-ketoglutarate- and Fe

In vivo phagocytosis and hematology in Astyanax altiparanae, a potential model for surrogate technology / Fagocitose in vivo e hematologia em Astyanax altiparanae, um potencial modelo para tecnologia de propagação mediada

Abstract Although the potential of surrogate propagation technology for aquaculture and conservation of Neotropical fish, the poor understanding of the host immune system may results in rejection and destruction of the donor material. Thus, it is necessary to study and to develop methods to evaluate the effects of immunosuppressive drugs employment and to evaluate the immunocompatibility between donor and receptor. Thus, the present study aimed to optimize a methodology to assess in vivo phagocytosis in Astyanax altiparanae using Saccharomyces cerevisiae and to evaluate their hematological response resultant from the inflammatory induction. To this, S. cerevisiae were labeled with Congo red and injected in the coelomic cavity of A. altiparanae at the concentration of 2.5 x 106 cells mL-1. A PBS solution and a non-injected group were kept as control. Fish blood was sampled and the phagocytic capacity and index were determined at 1, 2, 3 and 6 h post-injection (hpi). The yeast injection successfully stimulated phagocytosis, with the best result for phagocytosis assessment after 2 hpi. Moreover, it was achieved a high traceability of phagocytized and non-phagocytized yeast under optic microscopy analysis due to the Congo red labeling. The hematological profile was similar to usually observed in early infections, indicating lymphocyte migration to inflammatory site and increase in number of circulating phagocytes due to natural response to inflammatory stimulus. In conclusion, our method was efficient to assess in vivo phagocytosis in A. altiparanae and will be an important tool to evaluate the efficacy of immunosuppressive drugs in this species. Additionally, these results may serve as support for further studies in fish immunocompetence, both in laboratory and in field conditions.

Resumo Apesar do potencial apresentado pela tecnologia de propagação mediada para a aquicultura e conservação de peixes Neotropicais, o pobre entendimento do sistema imune do hospedeiro pode resultar na rejeição e destruição do material do doador. Com isso, se fazem necessários o estudo e o desenvolvimento de métodos para análise tanto dos efeitos de drogas imunossupressoras quanto para a avaliação da imunocompatibilidade entre doadores e receptores. Logo, o presente estudo teve como objetivo aperfeiçoar um método para analisar a fagocitose in vivo em Astyanax altiparanae usando Saccharomyces cerevisiae marcado e avaliar seu perfil hematológico resultante da indução inflamatória. Para isso, S. cerevisiae foram marcados com vermelho Congo e injetados na cavidade celomática dos A. altiparanae na concentração de 2,5 x 106 células.mL-1. Peixes injetados com PBS e peixes não injetados foram mantidos como controle. Sangue foi colhido e a capacidade fagocítica e o índice fagocítico foram determinados após 1, 2, 3 e 6 horas após à injeção (hpi). A injeção de levedura estimulou a fagocitose com sucesso, com o melhor resultado atingido após 2 hpi. Ainda, foi observada uma alta rastreabilidade das leveduras fagocitadas e não fagocitadas sob microscopia óptica devido à marcação com vermelho Congo. O perfil hematológico foi similar ao observado usualmente em infecções recém-induzidas, indicando migração de linfócitos ao sítio inflamatório e aumento no número de fagócitos circulantes devido à resposta natural ao estímulo inflamatório. Como conclusão, nosso método foi eficiente para analisar a fagocitose in vivo em A. altiparanae e será uma ferramenta importante para a avaliação de eficácia de drogas imunossopressoras para esta espécie. Em adição, estes resultados podem contribuir para futuros estudos em imunocompetência em peixes, tanto em âmbito laboratorial quanto a campo.

Innate Lymphoid Cells in the Airways: Their Functions and Regulators

Since the airways are constantly exposed to various pathogens and foreign antigens, various kinds of cells in the airways—including structural cells and immune cells—interact to form a precise defense system against pathogens and antigens that involve both innate immunity and acquired immunity. Accumulating evidence suggests that innate lymphoid cells (ILCs) play critical roles in the maintenance of tissue homeostasis, defense against pathogens and the pathogenesis of inflammatory diseases, especially at body surface mucosal sites such as the airways. ILCs are activated mainly by cytokines, lipid mediators and neuropeptides that are produced by surrounding cells, and they produce large amounts of cytokines that result in inflammation. In addition, ILCs can change their phenotype in response to stimuli from surrounding cells, which enables them to respond promptly to microenvironmental changes. ILCs exhibit substantial heterogeneity, with different phenotypes and functions depending on the organ and type of inflammation, presumably because of differences in microenvironments. Thus, ILCs may be a sensitive detector of microenvironmental changes, and analysis of their phenotype and function at local sites may enable us to better understand the microenvironment in airway diseases. In this review, we aimed to identify molecules that either positively or negatively influence the function and/or plasticity of ILCs and the sources of the molecules in the airways in order to examine the pathophysiology of airway inflammatory diseases and facilitate the issues to be solved.

Damaged male germ cells induce epididymitis in mice / 亚洲男科学杂志(英文版)

Epididymitis can be caused by infectious and noninfectious etiological factors. While microbial infections are responsible for infectious epididymitis, the etiological factors contributing to noninfectious epididymitis remain to be defined. The present study demonstrated that damaged male germ cells (DMGCs) induce epididymitis in mice. Intraperitoneal injection of the alkylating agent busulfan damaged murine male germ cells. Epididymitis was observed in mice 4 weeks after the injection of busulfan and was characterized by massive macrophage infiltration. Epididymitis was coincident with an accumulation of DMGCs in the epididymis. In contrast, busulfan injection into mice lacking male germ cells did not induce epididymitis. DMGCs induced innate immune responses in epididymal epithelial cells (EECs), thereby upregulating the pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β), as well as the chemokines such as monocyte chemotactic protein-1 (MCP-1), monocyte chemotactic protein-5 (MCP-5), and chemokine ligand-10 (CXCL10). These results suggest that male germ cell damage may induce noninfectious epididymitis through the induction of innate immune responses in EECs. These findings provide novel insights into the mechanisms underlying noninfectious epididymitis, which might aid in the diagnosis and treatment of the disease.

Dephosphorylation of cGAS by PPP6C impairs its substrate binding activity and innate antiviral response

The cyclic GMP-AMP (cGAMP) synthase (cGAS) plays a critical role in host defense by sensing cytosolic DNA derived from microbial pathogens or mis-located cellular DNA. Upon DNA binding, cGAS utilizes GTP and ATP as substrates to synthesize cGAMP, leading to MITA-mediated innate immune response. In this study, we identified the phosphatase PPP6C as a negative regulator of cGAS-mediated innate immune response. PPP6C is constitutively associated with cGAS in un-stimulated cells. DNA virus infection causes rapid disassociation of PPP6C from cGAS, resulting in phosphorylation of human cGAS S435 or mouse cGAS S420 in its catalytic pocket. Mutation of this serine residue of cGAS impairs its ability to synthesize cGAMP upon DNA virus infection. In vitro experiments indicate that S420-phosphorylated mcGAS has higher affinity to GTP and enzymatic activity. PPP6C-deficiency promotes innate immune response to DNA virus in various cells. Our findings suggest that PPP6C-mediated dephosphorylation of a catalytic pocket serine residue of cGAS impairs its substrate binding activity and innate immune response, which provides a mechanism for keeping the DNA sensor cGAS inactive in the absence of infection to avoid autoimmune response.

Dephosphorylation of cGAS by PPP6C impairs its substrate binding activity and innate antiviral response

The cyclic GMP-AMP (cGAMP) synthase (cGAS) plays a critical role in host defense by sensing cytosolic DNA derived from microbial pathogens or mis-located cellular DNA. Upon DNA binding, cGAS utilizes GTP and ATP as substrates to synthesize cGAMP, leading to MITA-mediated innate immune response. In this study, we identified the phosphatase PPP6C as a negative regulator of cGAS-mediated innate immune response. PPP6C is constitutively associated with cGAS in un-stimulated cells. DNA virus infection causes rapid disassociation of PPP6C from cGAS, resulting in phosphorylation of human cGAS S435 or mouse cGAS S420 in its catalytic pocket. Mutation of this serine residue of cGAS impairs its ability to synthesize cGAMP upon DNA virus infection. In vitro experiments indicate that S420-phosphorylated mcGAS has higher affinity to GTP and enzymatic activity. PPP6C-deficiency promotes innate immune response to DNA virus in various cells. Our findings suggest that PPP6C-mediated dephosphorylation of a catalytic pocket serine residue of cGAS impairs its substrate binding activity and innate immune response, which provides a mechanism for keeping the DNA sensor cGAS inactive in the absence of infection to avoid autoimmune response.

cGAS enhances the HTLV-1 reverse transcription intermediate ssDNA90-induced innate immune re-sponses / 中华微生物学和免疫学杂志

Objective To investigate the role of cyclic GMP-AMP synthase (cGAS),a cytosolic DNA sensor,in regulating innate immune responses induced by reverse transcription intermediate of human T cell leukemia virus type 1 (HTLV-1). Methods (1)ssDNA90,the reverse transcription intermediate of HTLV-1,was transfected into HeLa cells to observe changes in the expression pattern of cGAS in transfected-HeLa cells with immunoblot assay. (2) HeLa cells were firstly transfected with cGAS-encoding plasmid and then ssDNA90 24 hours later. Real-time PCR was used to measure the expression of interferon ( IFN)-β, IFN-gamma-inducible protein 10 ( IP-10 ), regulated on activation, normal T cell expressed and secreted (RANTES) and tumor necrosis factor (TNF)-α. Immunoblot assay was performed to measure phosphorylated interferon regulatory factor 3 (IRF3) and p65. (3)cGAS expression was silenced by siRNA in HeLa and phorbol-12-myristate-13-acetate (PMA)-treated THP1 (PMA-THP1) cells and then ssDNA90 was transfect-ed into these cells 24 hours later. Real-time PCR was used to measure the expression of IFN-β,IP-10,RAN-TES and TNF-α. Immunoblot assay was performed to measure phosphorylated IRF3 and p65. Results Ex-pression of cGAS was increased in HeLa cells after ssDNA90 transfection. Compared with control cells, cGAS-transfected HeLa cells showed increased expression of IFN-β, IP-10, RANTES and TNF-α and en-hanced phosphorylation of IRF3 and p65 after ssDNA90 transfection. Compared with control cells,both HeLa and PMA-THP1 cells with silenced expression of cGAS showed impaired production of IFN-β,IP-10,RAN-TES and TNF-α after ssDNA90 transfection. Moreover,ssDNA90-induced phosphorylation of IRF3 and p65 were decreased after cGAS gene-knockdown. Conclusion cGAS might promote HTLV-1 RTI ssDNA90-in-duced innate immune responses.

Classical and alternative macrophages have impaired function during acute and chronic HIV-1 infection

Abstract Objectives: Three decades after HIV recognition and its association with AIDS development, many advances have emerged – especially related to prevention and treatment. Undoubtedly, the development of Highly Active Antiretroviral Therapy (HAART) dramatically changed the future of the syndrome that we know today. In the present study, we evaluate the impact of Highly Active Antiretroviral Therapy on macrophage function and its relevance to HIV pathogenesis. Methods: PBMCs were isolated from blood samples and monocytes (CD14+ cells) were purified. Monocyte-Derived Macrophages (MDMs) were activated on classical (MGM-CSF+IFN-γ) or alternative (MIL-4+IL13) patterns using human recombinant cytokines for six days. After this period, Monocyte-Derived Macrophages were stimulated with TLR2/Dectin-1 or TLR4 agonists and we evaluated the influence of HIV-1 infection and Highly Active Antiretroviral Therapy on the release of cytokines/chemokines by macrophages. Results: The data were obtained using Monocyte-Derived Macrophages derived from HIV naïve or from patients on regular Highly Active Antiretroviral Therapy. Classically Monocyte-Derived Macrophages obtained from HIV-1 infected patients on Highly Active Antiretroviral Therapy released higher levels of IL-6 and IL-12 even without PAMPs stimuli when compared to control group. On the other hand, alternative Monocyte-Derived Macrophages derived from HIV-1 infected patients on Highly Active Antiretroviral Therapy released lower levels of IL-6, IL-10, TNF-α, IP-10 and RANTES after LPS stimuli when compared to control group. Furthermore, healthy individuals have a complex network of cytokines/chemokines released by Monocyte-Derived Macrophages after PAMP stimuli, which was deeply affected in MDMs obtained from naïve HIV-1 infected patients and only partially restored in MDMs derived from HIV-1 infected patients even on regular Highly Active Antiretroviral Therapy. Conclusion: Our therapy protocols were not effective in restoring the functional alterations induced by HIV, especially those found on macrophages. These findings indicate that we still need to develop new approaches and improve the current therapy protocols, focusing on the reestablishment of cellular functions and prevention/treatment of opportunistic infections.

In vivo phagocytosis and hematology in Astyanax altiparanae, a potential model for surrogate technology

Abstract Although the potential of surrogate propagation technology for aquaculture and conservation of Neotropical fish, the poor understanding of the host immune system may results in rejection and destruction of the donor material. Thus, it is necessary to study and to develop methods to evaluate the effects of immunosuppressive drugs employment and to evaluate the immunocompatibility between donor and receptor. Thus, the present study aimed to optimize a methodology to assess in vivo phagocytosis in Astyanax altiparanae using Saccharomyces cerevisiae and to evaluate their hematological response resultant from the inflammatory induction. To this, S. cerevisiae were labeled with Congo red and injected in the coelomic cavity of A. altiparanae at the concentration of 2.5 x 106 cells mL-1. A PBS solution and a non-injected group were kept as control. Fish blood was sampled and the phagocytic capacity and index were determined at 1, 2, 3 and 6 h post-injection (hpi). The yeast injection successfully stimulated phagocytosis, with the best result for phagocytosis assessment after 2 hpi. Moreover, it was achieved a high traceability of phagocytized and non-phagocytized yeast under optic microscopy analysis due to the Congo red labeling. The hematological profile was similar to usually observed in early infections, indicating lymphocyte migration to inflammatory site and increase in number of circulating phagocytes due to natural response to inflammatory stimulus. In conclusion, our method was efficient to assess in vivo phagocytosis in A. altiparanae and will be an important tool to evaluate the efficacy of immunosuppressive drugs in this species. Additionally, these results may serve as support for further studies in fish immunocompetence, both in laboratory and in field conditions.

Resumo Apesar do potencial apresentado pela tecnologia de propagação mediada para a aquicultura e conservação de peixes Neotropicais, o pobre entendimento do sistema imune do hospedeiro pode resultar na rejeição e destruição do material do doador. Com isso, se fazem necessários o estudo e o desenvolvimento de métodos para análise tanto dos efeitos de drogas imunossupressoras quanto para a avaliação da imunocompatibilidade entre doadores e receptores. Logo, o presente estudo teve como objetivo aperfeiçoar um método para analisar a fagocitose in vivo em Astyanax altiparanae usando Saccharomyces cerevisiae marcado e avaliar seu perfil hematológico resultante da indução inflamatória. Para isso, S. cerevisiae foram marcados com vermelho Congo e injetados na cavidade celomática dos A. altiparanae na concentração de 2,5 x 106 células.mL-1. Peixes injetados com PBS e peixes não injetados foram mantidos como controle. Sangue foi colhido e a capacidade fagocítica e o índice fagocítico foram determinados após 1, 2, 3 e 6 horas após à injeção (hpi). A injeção de levedura estimulou a fagocitose com sucesso, com o melhor resultado atingido após 2 hpi. Ainda, foi observada uma alta rastreabilidade das leveduras fagocitadas e não fagocitadas sob microscopia óptica devido à marcação com vermelho Congo. O perfil hematológico foi similar ao observado usualmente em infecções recém-induzidas, indicando migração de linfócitos ao sítio inflamatório e aumento no número de fagócitos circulantes devido à resposta natural ao estímulo inflamatório. Como conclusão, nosso método foi eficiente para analisar a fagocitose in vivo em A. altiparanae e será uma ferramenta importante para a avaliação de eficácia de drogas imunossopressoras para esta espécie. Em adição, estes resultados podem contribuir para futuros estudos em imunocompetência em peixes, tanto em âmbito laboratorial quanto a campo.

Locations of TLR4 in healthy dental pulp tissue and dental pulp tissue affected by deep caries / 口腔疾病防治

Objective@#To analyze the role of TLR4 in innate immune response of dental pulp by comparing the locations and expressions of TLR4 in healthy dental pulp tissue and dental pulp tissue affected by deep caries. @*Methods @# Healthy teeth and teeth affected by deep caries were demineralized and stained with hematoxylin and eosin (HE) to observe the morphology of dental pulp. Immunohistochemistry staining was performed to observe the expressions of TLR4.@*Results @# Observed under HE staining, dentin tubules of teeth affected by deep caries were damaged with a lot bacteria mass. The expression of TLR4 were located in the odontoblast layer and near the blood vessels in both groups. Positive staining of TLR4 in deep caries pulps (2.10±0.74) were significantly higher than that in healthy teeth (1.25 ±0.46). @*Conclusion @#Expression of TLR4 in deep caries pulp is stronger than that in healthy pulp. It suggests that TLR4 may play a role in the innate immune response of deep caries.

The Relationship between Mitochondria and NLRP3 Inflammasome

Mitochondria participate in various intracellular metabolic pathways such as generating intracellular ATP, synthesizing several essential molecules, regulating calcium homeostasis, and producing the cell's reactive oxygen species (ROS). Emerging studies have demonstrated newly discovered roles of mitochondria, which participate in the regulation of innate immune responses by modulating NLRP3 inflammasomes. Here, we review the recently proposed pathways to be involved in mitochondria-mediated regulation of inflammasome activation and inflammation: 1) mitochondrial ROS, 2) calcium mobilization, 3) nicotinamide adenine dinucleotide (NAD+) reduction, 4) cardiolipin, 5) mitofusin, 6) mitochondrial DNA, 7) mitochondrial antiviral signaling protein. Furthermore, we highlight the significance of mitophagy as a negative regulator of mitochondrial damage and NLRP3 inflammasome activation, as potentially helpful therapeutic approaches which could potentially address uncontrolled inflammation.

TLR/MyD88-mediated Innate Immunity in Intestinal Graft-versus-Host Disease

Graft-versus-host disease (GHVD) is a severe complication after allogeneic hematopoietic stem cell transplantation. The degree of inflammation in the gastrointestinal tract, a major GVHD target organ, correlates with the disease severity. Intestinal inflammation is initiated by epithelial damage caused by pre-conditioning irradiation. In combination with damages caused by donor-derived T cells, such damage disrupts the epithelial barrier and exposes innate immune cells to pathogenic and commensal intestinal bacteria, which release ligands for Toll-like receptors (TLRs). Dysbiosis of intestinal microbiota and signaling through the TLR/myeloid differentiation primary response gene 88 (MyD88) pathways contribute to the development of intestinal GVHD. Understanding the changes in the microbial flora and the roles of TLR signaling in intestinal GVHD will facilitate the development of preventative and therapeutic strategies.

Escaping mechanism from innate immunity mediated clearance by high pathogenic influenza virus during infection / 中国免疫学杂志

Severe influenza infection is usually associated with hypercytokinemia ,but the type Ⅰ Interferon remains at low lever or absence.The regulatory mechanism on or the immune escaping mechanism from type I interferon by virus remains to be deter -mined.We briefly summarized the progress in this field and raise several questions to be addressed in the future .

Role of NKG2 receptors-mediated natural killer cell activation in chronic HBV infection / 中华临床感染病杂志

The activation of NK cell , mediated by natural killer group 2 ( NKG2 ) family receptor , plays an important role in antiviral immune response and disease progression after hepatitis B virus (HBV) infection.To explore the NKG2 receptors-mediated NK cell activation and its mechanism may be of value for anti-HBV targeting immune treatment .This article reviews the recent research progress on the role of NK cells and its NKG2 family receptors in immunity of chronic HBV infection and its mechanisms .

Effects of in utero exposure to inflammation on innate immune response in preterm infants / 临床儿科杂志

Objective To explore the effect of in utero exposure to inlfammation on innate immune response in preterm infants. Methods Forty-seven premature infants with gestational age<35 weeks were recruited in this study. According to his-tological evidence of placental infection, all neonates were divided into intrauterine inlfammation positive group and negative group. Mononuclear cells and monocytes were isolated from umbilical cord blood, and were cultured in vitro in the presence or absence of LPS (100 ng/ml). The levels of interleukin 1β(IL-1β), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α) and interleukin 10 (IL-10) in cord blood plasma and monocyte cultural supernatants were measured by ELISA respectively. The level of IL-1β, TNF-α, IL-6 and IL-10 mRNA were detected by Real-time PCR. Expression of HLA-DR on surface of CD14+monocytes and ratio of CD3+CD4+/CD3+CD8+T was analyzed by lfow cytometry. Results (1) The level of cord plasma IL-6 in intrauterine inlfammation positive group was signiifcantly higher than in negative group. (P=0.02). (2) After stimulation of LPS, levels of IL-1β, IL-6, TNF-α, IL-10 in supernatants were increased signiifcantly, in consistence with their mRNA expression (P<0.05) in both groups. (3) Expression of HLA-DR on surface of monocytes was signiifcantly decreased after stimulation with LPS in intrauterine inlfammation positive group (P=0.012), but was signiifcantly increased in negative group (P=0.0305). Con-clusions In utero exposure to inlfammation does not suppress the response of monocytes to LPS in preterm neonates, but impairs the antigen presenting function in monocytes.

Cloning, expression and functional analysis of the duck Toll-like receptor 5 (TLR5) gene

Toll-like receptor 5 (TLR5) is responsible for the recognition of bacterial flagellin in vertebrates. In the present study, the first TLR5 gene in duck was cloned. The open reading frame (ORF) of duck TLR5 (dTLR5) cDNA is 2580 bp and encodes a polypeptide of 859 amino acids. We also cloned partial sequences of myeloid differentiation factor 88, 2'-5'-oligoadenylate synthetase (OAS), and myxovirus resistance (Mx) genes from duck. dTLR5 mRNA was highly expressed in the bursa of Fabricius, spleen, trachea, lung, jejunum, rectum, and skin; moderately expressed in the muscular and glandular tissues, duodenum, ileum, caecum, and pancreas; and minimally expressed in the heart, liver, kidney, and muscle. DF-1 or HeLa cells transfected with DNA constructs encoding dTLR5 can activate NF-kappaB leading to the activation of interleukin-6 (IL-6) promoter. When we challenged ducks with a Herts33 Newcastle disease virus (NDV), mRNA transcription of the antiviral molecules Mx, Double stranded RNA activated protein kinase (PKR), and OAS was up-regulated in the liver, lung, and spleen 1 and 2 days post-inoculation.

Aspectos de la respuesta inmune innata en las infecciones intramamarias causadas por Staphylococcus aureus en bovinos / Aspects of the innate immune response to intramammary Staphylococcus aureus infections in cattle

Staphylococcus aureus es el principal agente causante de mastitis bovina en Argentina y en el mundo. Esta bacteria ocasiona infecciones crónicas que generan importantes pérdidas a los productores y la industria lechera. El objetivo de este artículo es caracterizar los mecanismos que intervienen en la infección causada por S. aureus en la glándula mamaria bovina, evaluando dos aspectos diferentes del proceso infeccioso: por un lado, lo vinculado con la respuesta inmune innata por parte del hospedador, y por otro, la capacidad de la bacteria para evadir el sistema inmune e interactuar con diferentes tipos celulares. La exploración de la interacción de S. aureus con el sistema inmune de la glándula mamaria bovina permitirá identificar blancos para delinear nuevas alternativas preventivas o curativas, que contribuyan a evitar o eliminar las infecciones causadas por este organismo

Staphylococcus aureus is the pathogen most frequently isolated from bovine mastitis worldwide, causing chronic intramammary infections that limit profitable dairying. The objective of this article is to characterize the mechanisms involved in S. aureus mammary gland infections considering two different aspects of the infectious process; on the one hand, the aspects involved in the host innate immune response and on the other hand, the capacity of this organism to evade the immune system and interact with different cell types. The exploration of S. aureus interactions with the immune response of bovine mammary gland will help identify targets to outline new preventive or curative alternatives for intramammary infections caused by this organism

The rapid and sustained responses of dendritic cells to influenza virus infection in a non-human primate model

Dendritic cells (DCs) are readily infected by influenza viruses and play a crucial role in regulating host innate and adaptive immune responses to viral infection. The aims of this study are to characterize the dynamic changes in the numbers and maturation status of dendritic cells present in the lung and lung-associated lymph nodes (LALNs) in the model of a non-human primate (NHP) infected by influenza A virus (IAV). Cynomolgus macaques were infected with influenza A virus (H3N2) via bronchoscopy. Flow cytometry was used to analyze the DC numbers, maturation status and subsets during the time of acute infection (days 1, 2, 3, 4, 7) and the resolution phase (day 30). A dramatic increase in the numbers of influenza A virus-infected CD11c+CD14- myeloid dendritic cells (mDCs) and CD11c-CD123+ plasmacytoid dendritic cells (pDCs) were observed from day 1 to day 4 and peak up from day 7 post-infection. In lung and lung-associated lymph nodes, the numbers and maturation status of myeloid dendritic cells and plasmacytoid dendritic cells increased more slowly than those in the lung tissues. On day 30 post-infection, influenza A virus challenge increased the number of myeloid dendritic cells, but not plasmacytoid dendritic cells, compared with baseline. These findings indicate that dendritic cells are susceptible to influenza A virus infection, with the likely purpose of increasing mature myeloid dendritic cells numbers in the lung and lung and lung-associated lymph nodes, which provides important new insights into the regulation of dendritic cells in a non-human primate model.

Inactivated Parapoxvirus ovis induces a transient increase in the expression of proinflammatory, Th1-related, and autoregulatory cytokines in mice

The immunostimulatory properties of inactivated Parapoxvirus ovis (iPPVO) have long been investigated in different animal species and experimental settings. In this study, we investigated the effects of iPPVO on cytokine expression in mice after intraperitoneal inoculation. Spleen and sera collected from iPPVO-treated mice at intervals after inoculation were submitted to cytokine mRNA determination by real-time PCR (qPCR), serum protein concentration by ELISA, and interferon (IFN)-α/β activity by bioassay. The spleen of iPPVO-treated animals showed a significant increase in mRNA expression of all cytokines assayed, with different kinetics and magnitude. Proinflammatory cytokines interleukin (IL)-1β, tumor necrosis factor-alpha (TNF-α), and IL-8 mRNA peaked at 24 hours postinoculation (hpi; 5.4-fold increase) and 48 hpi (3- and 10-fold increases), respectively. A 15-fold increase in IFN-γ and 6-fold IL-12 mRNA increase were detected at 48 and 24 hpi, respectively. Increased expression of autoregulatory cytokines (Th2), mainly IL-10 and IL-4, could be detected at later times (72 and 96 hpi) with peaks of 4.7- and 4.9-fold increases, respectively. IFN-I antiviral activity against encephalomyocarditis virus was demonstrated in sera of treated animals between 6 and 12 hpi, with a >90% reduction in the number of plaques. Measurement of serum proteins by ELISA revealed increased levels of IL-1, TNF-α, IL-12, IFN-γ, and IL-10, with kinetics similar to those observed by qPCR, especially for IL-12 and IFN-γ. These data demonstrate that iPPVO induced a transient and complex cytokine response, initially represented by Th1-related cytokines followed by autoregulatory and Th2 cytokines.