Inflammasome recognition of influenza virus is essential for adaptive immune responses

By T. Ichinohe, H. Lee, Y. Ogura, R. Flavell, A. Iwasaki. Journal of Experimental Medicine, 2009

731 citations recorded by the source corpus.

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.

Subfields: Epidemiology, Immunology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/a78ef70ff40fe8eefc5db9391be4f63c675e8ed3

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Epidemiology

1. Olivier Schwartz
2. M. Lamkanfi
3. M. Albert
4. A. Iwasaki
5. Haitao Wen
6. T. Kanneganti
7. J. Ting

In Immunology

1. M. Lamkanfi
2. T. Kanneganti
3. Olivier Schwartz
4. M. Albert
5. A. Iwasaki
6. K. Boyd
7. N. Regamey
8. M. Edwards

In Molecular Biology

1. T. Kanneganti
2. M. Lamkanfi
3. K. Boyd
4. A. Iwasaki
5. B. Davis
6. Haitao Wen
7. N. Regamey
8. M. Edwards

Citations in the corpus

• Microbiota regulates immune defense against respiratory tract influenza A virus infection (2011, methodology): “Adaptive immunity following respiratory infection with influenza virus requires the inflammasome activation (6).”
• Biology and pathogenesis of chikungunya virus (2010, background): “There has been a surge of new information regarding the role of the inflammasome , which is well recognized as being crucial for IL-1β production following bacterial infection and also seems to participate in the control of viruse”
• The Inflammasome NLRs in Immunity, Inflammation, and Associated Diseases (2011, background): “During in vivo infection with low doses of influenza A, NLRP3 is dispensable for host survival (62); however, at high doses of influenza A, NLRP3 is central in recruiting inflammatory cells to the lungs (15, 63).”
• The Airway Epithelium: Soldier in the Fight against Respiratory Viruses (2011, background): “While NOD1 and NOD2, the first NLRs identified, are involved mainly in the recognition of bacterial peptidoglycans, NLRP3 seems to be important for the immune response to respiratory viruses (5, 118, 192, 280).”
• Redox Regulation of NLRP3 Inflammasomes: ROS as Trigger or Effector? (2015, neutral): “With regard to exogenous NLRP3 inflammasome activators, many studies have provided evidence of NLRP3 inflammasome activation in response to a whole host of foreign danger signals and microbes, including the influenza virus, adenoviruses, Staphylococcus aureus, Escherichia coli, Neisseria gonorrhoe, ”
• NLRP3 (NALP3/CIAS1/Cryopyrin) mediates key innate and healing responses to influenza A virus via the regulation of caspase-1 (2009, positive): “Another study has also found a role for Cryopyrin in influenza-induced IL-1b production, although only from a subset of cell types, with caspase-1 playing a more prominent role (Ichinohe et al., 2009).”
• Activation of innate immune antiviral response by NOD2 (2009, background): “In addition to Nod2, cryopyrin (Nalp3), another NLR protein, activates the inflammasome and leads to IL-1 production after stimulation with bacterial and viral (influenza A) RN”