Clin Exp Vaccine Res.  2014 Jan;3(1):5-11. 10.7774/cevr.2014.3.1.5.

Inflammasomes in antiviral immunity: clues for influenza vaccine development

• Yamazaki T
• Ichinohe T

• KMID: 2049091
• DOI: http://doi.org/10.7774/cevr.2014.3.1.5

Abstract

Inflammasomes are cytosolic multiprotein complexes that sense microbial motifs or cellular stress and stimulate caspase-1-dependent cytokine secretion and cell death. Recently, it has become increasingly evident that both DNA and RNA viruses activate inflammasomes, which control innate and adaptive immune responses against viral infections. In addition, recent studies suggest that certain microbiota induce inflammasomes-dependent adaptive immunity against influenza virus infections. Here, we review recent advances in research into the role of inflammasomes in antiviral immunity.

Keyword

Orthomyxoviridae; Human NLRP3 protein; Metagenome; Dendritic cells

MeSH Terms

Adaptive Immunity
Cell Death
Cytosol
Dendritic Cells
DNA
Inflammasomes*
Influenza Vaccines*
Influenza, Human*
Metagenome
Microbiota
Multiprotein Complexes
Orthomyxoviridae
RNA Viruses
DNA
Inflammasomes
Influenza Vaccines
Multiprotein Complexes

Figure

• 

  Fig. 1 Recognition of RNA viruses by nucleotide-binding domain and leucine-rich-repeat-containing protein 3 (NLRP3) inflammasome. The NLRP3 recognizes the disturbances in intracellular ionic concentrations induced by viroporins from respiratory syncytial virus (RSV), encephalomyocarditis virus (EMCV), poliovirus, enterovirus 71 (EV71), human rhinovirus (HRV), or influenza virus. Measles virus V protein inhibits activation of NLRP3 inflammasome by interacting with the NLRP3. The RNA helicase DHX33 binds to cytosolic double-stranded RNAs (dsRNAs) to trigger NLRP3 inflammasome activation. After activation of the NLRP3, it recruits apoptosis-associated speck-like protein containing a CARD (ASC) that, in turn, recruits pro-caspase-1, which is activated by autocatalytic cleavage. Cleaved caspase-1 catalyses proteolytic processing of pro-interleukin (IL)-1β and pro-IL-18 into the active forms and stimulates their secretion. ER, endoplasmic reticulum; SH, small hydrophobic.

• 

  Fig. 2 Proposed model of inflammasome-dependent induction of adaptive immunity against influenza virus infection. Activation of caspase-1 in influenza virus-infected respiratory dendritic cells (DCs) stimulates secretion of interleukin-1 beta (IL-1β) and triggers a form of cells death, known as pyroptosis. Bystander DCs activated by inflammatory signals capture viral antigens (vAg) and migrate from the lung to the mediastinal lymph nodes (mLNs) to prime naïve CD8 T cells. Gut-resident microbiota provides signals leading to the expression of mRNA for pro-IL-1β, pro-IL-18, and NLRP3 at steady state. NLRP3, nucleotide-binding domain and leucine-rich-repeat-containing protein 3.

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