scholarly journals Inflammasome recognition of influenza virus is essential for adaptive immune responses

2009 ◽  
Vol 206 (1) ◽  
pp. 79-87 ◽  
Author(s):  
Takeshi Ichinohe ◽  
Heung Kyu Lee ◽  
Yasunori Ogura ◽  
Richard Flavell ◽  
Akiko Iwasaki
Keyword(s):  
Influenza Virus ◽  
T Cell ◽  
Virus Infection ◽  
Adaptive Immunity ◽  
Influenza Virus Infection ◽  
Type I Interferons ◽  
Inflammasome Activation ◽  
Type I ◽  
Stromal Compartment ◽  
Caspase 1

Influenza virus infection is recognized by the innate immune system through Toll like receptor (TLR) 7 and retinoic acid inducible gene I. These two recognition pathways lead to the activation of type I interferons and resistance to infection. In addition, TLR signals are required for the CD4 T cell and IgG2a, but not cytotoxic T lymphocyte, responses to influenza virus infection. In contrast, the role of NOD-like receptors (NLRs) in viral recognition and induction of adaptive immunity to influenza virus is unknown. We demonstrate that respiratory infection with influenza virus results in the activation of NLR inflammasomes in the lung. Although NLRP3 was required for inflammasome activation in certain cell types, CD4 and CD8 T cell responses, as well as mucosal IgA secretion and systemic IgG responses, required ASC and caspase-1 but not NLRP3. Consequently, ASC, caspase-1, and IL-1R, but not NLRP3, were required for protective immunity against flu challenge. Furthermore, we show that caspase-1 inflammasome activation in the hematopoietic, but not stromal, compartment was required to induce protective antiviral immunity. These results demonstrate that in addition to the TLR pathways, ASC inflammasomes play a central role in adaptive immunity to influenza virus.

scholarly journals Immunopathogenesis of SARS-CoV-2-induced pneumonia: lessons from influenza virus infection

2020 ◽  
Vol 40 (1) ◽  
Author(s):  
Masaaki Miyazawa
Keyword(s):  
Influenza Virus ◽  
T Cell ◽  
Virus Infection ◽  
Tissue Injury ◽  
Influenza Virus Infection ◽  
T Cell Responses ◽  
Type I ◽  
Upper Respiratory Tract ◽  
Viral Spread ◽  
Cell Responses

Abstract Factors determining the progression of frequently mild or asymptomatic severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection into life-threatening pneumonia remain poorly understood. Viral and host factors involved in the development of diffuse alveolar damage have been extensively studied in influenza virus infection. Influenza is a self-limited upper respiratory tract infection that causes acute and severe systemic symptoms and its spread to the lungs is limited by CD4+ T-cell responses. A vicious cycle of CCL2- and CXCL2-mediated inflammatory monocyte and neutrophil infiltration and activation and resultant massive production of effector molecules including tumor necrosis factor (TNF)-α, nitric oxide, and TNF-related apoptosis-inducing ligand are involved in the pathogenesis of progressive tissue injury. SARS-CoV-2 directly infects alveolar epithelial cells and macrophages and induces foci of pulmonary lesions even in asymptomatic individuals. Mechanisms of tissue injury in SARS-CoV-2-induced pneumonia share some aspects with influenza virus infection, but IL-1β seems to play more important roles along with CCL2 and impaired type I interferon signaling might be associated with delayed virus clearance and disease severity. Further, data indicate that preexisting memory CD8+ T cells may play important roles in limiting viral spread in the lungs and prevent progression from mild to severe or critical pneumonia. However, it is also possible that T-cell responses are involved in alveolar interstitial inflammation and perhaps endothelial cell injury, the latter of which is characteristic of SARS-CoV-2-induced pathology.

scholarly journals Influenza Virus Evades Innate and Adaptive Immunity via the NS1 Protein

2006 ◽  
Vol 80 (13) ◽  
pp. 6295-6304 ◽  
Author(s):  
Ana Fernandez-Sesma ◽  
Svetlana Marukian ◽  
Barbara J. Ebersole ◽  
Dorothy Kaminski ◽  
Man-Seong Park ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Influenza Virus ◽  
Virus Infection ◽  
Adaptive Immunity ◽  
Influenza A Virus ◽  
Influenza A ◽  
Influenza Virus Infection ◽  
Type I ◽  
Ns1 Protein ◽  
Dc Maturation

ABSTRACT Both antibodies and T cells contribute to immunity against influenza virus infection. However, the generation of strong Th1 immunity is crucial for viral clearance. Interestingly, we found that human dendritic cells (DCs) infected with influenza A virus have lower allospecific Th1-cell stimulatory abilities than DCs activated by other stimuli, such as lipopolysaccharide and Newcastle disease virus infection. This weak stimulatory activity correlates with a suboptimal maturation of the DCs following infection with influenza A virus. We next investigated whether the influenza A virus NS1 protein could be responsible for the low levels of DC maturation after influenza virus infection. The NS1 protein is an important virulence factor associated with the suppression of innate immunity via the inhibition of type I interferon (IFN) production in infected cells. Using recombinant influenza and Newcastle disease viruses, with or without the NS1 gene from influenza virus, we found that the induction of a genetic program underlying DC maturation, migration, and T-cell stimulatory activity is specifically suppressed by the expression of the NS1 protein. Among the genes affected by NS1 are those coding for macrophage inflammatory protein 1β, interleukin-12 p35 (IL-12 p35), IL-23 p19, RANTES, IL-8, IFN-α/β, and CCR7. These results indicate that the influenza A virus NS1 protein is a bifunctional viral immunosuppressor which inhibits innate immunity by preventing type I IFN release and inhibits adaptive immunity by attenuating human DC maturation and the capacity of DCs to induce T-cell responses. Our observations also support the potential use of NS1 mutant influenza viruses as live attenuated influenza virus vaccines.

Obesity worsens the outcome of influenza virus infection associated with impaired type I interferon induction in mice

2019 ◽  
Vol 513 (2) ◽  
pp. 405-411 ◽  
Author(s):  
Ho Namkoong ◽  
Makoto Ishii ◽  
Hideki Fujii ◽  
Takahiro Asami ◽  
Kazuma Yagi ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Type I Interferon ◽  
Influenza Virus Infection ◽  
Type I ◽  
Interferon Induction

scholarly journals Deficiency of the NOD-Like Receptor NLRC5 Results in Decreased CD8+ T Cell Function and Impaired Viral Clearance

2017 ◽  
Vol 91 (17) ◽  
Author(s):  
Christopher R. Lupfer ◽  
Kate L. Stokes ◽  
Teneema Kuriakose ◽  
Thirumala-Devi Kanneganti
Keyword(s):  
T Cells ◽  
Influenza Virus ◽  
T Cell ◽  
Virus Infection ◽  
Adaptive Immune Response ◽  
Influenza Virus Infection ◽  
Viral Clearance ◽  
Mhc I ◽  
Adaptive Immune ◽  
Pathogen Recognition Receptors

ABSTRACT Pathogen recognition receptors are vital components of the immune system. Engagement of these receptors is important not only for instigation of innate immune responses to invading pathogens but also for initiating the adaptive immune response. Members of the NOD-like receptor (NLR) family of pathogen recognition receptors have important roles in orchestrating this response. The NLR family member NLRC5 regulates major histocompatibility complex class I (MHC-I) expression during various types of infections, but its role in immunity to influenza A virus (IAV) is not well studied. Here we show that Nlrc5 −/− mice exhibit an altered CD8+ T cell response during IAV infection compared to that of wild-type (WT) mice. Nlrc5 −/− mice have decreased MHC-I expression on hematopoietic cells and fewer CD8+ T cells prior to infection. NLRC5 deficiency does not affect the generation of antigen-specific CD8+ T cells following IAV infection; however, a change in epitope dominance is observed in Nlrc5 −/− mice. Moreover, IAV-specific CD8+ T cells from Nlrc5 −/− mice have impaired effector functions. This change in the adaptive immune response is associated with impaired viral clearance in Nlrc5 −/− mice. Collectively, our results demonstrate an important role for NLRC5 in regulation of antiviral immune responses and viral clearance during IAV infection. IMPORTANCE The NOD-like receptor family member NLRC5 is known to regulate expression of MHC-I as well as other genes required for antigen processing. In addition, NLRC5 also regulates various immune signaling pathways. In this study, we investigated the role of NLRC5 during influenza virus infection and found a major role for NLRC5 in restricting virus replication and promoting viral clearance. The observed increases in viral titers in NLRC5-deficient mice correlated with impaired effector CD8+ T cell responses. Although NLRC5-deficient mice were defective at clearing the virus, they did not show an increase in morbidity or mortality following influenza virus infection because of other compensatory immune mechanisms. Therefore, our study highlights how NLRC5 regulates multiple immune effector mechanisms to promote the host defense during influenza virus infection.

scholarly journals Residual Antigen Presentation after Influenza Virus Infection Affects CD8 T Cell Activation and Migration

Immunity ◽  
2006 ◽  
Vol 24 (4) ◽  
pp. 439-449 ◽  
Author(s):  
David J. Zammit ◽  
Damian L. Turner ◽  
Kimberly D. Klonowski ◽  
Leo Lefrançois ◽  
Linda S. Cauley
Keyword(s):  
Influenza Virus ◽  
T Cell ◽  
Virus Infection ◽  
Antigen Presentation ◽  
T Cell Activation ◽  
Cell Activation ◽  
Influenza Virus Infection ◽  
Cd8 T Cell ◽  
And Migration

scholarly journals Sterilizing immunity to influenza virus infection requires local antigen-specific T cell response in the lungs

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Avijit Dutta ◽  
Ching-Tai Huang ◽  
Chun-Yen Lin ◽  
Tse-Ching Chen ◽  
Yung-Chang Lin ◽  
...  
Keyword(s):  
Influenza Virus ◽  
T Cell ◽  
Virus Infection ◽  
Cell Response ◽  
Influenza Virus Infection ◽  
T Cell Response ◽  
Sterilizing Immunity
Sign in / Sign up

Export Citation Format

Share Document