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Review
. 2022 Mar 17:13:851835.
doi: 10.3389/fmicb.2022.851835. eCollection 2022.

Inflammasome Contribution to the Activation of Th1, Th2, and Th17 Immune Responses

Ekaterina Martynova  1 , Albert Rizvanov  1 , Richard A Urbanowicz  2 , Svetlana Khaiboullina  1
Affiliations
Review

Inflammasome Contribution to the Activation of Th1, Th2, and Th17 Immune Responses

Ekaterina Martynova et al. Front Microbiol. .

Abstract

Inflammasomes are cytosolic polyprotein complexes formed in response to various external and internal stimuli, including viral and bacterial antigens. The main product of the inflammasome is active caspase 1 which proteolytically cleaves, releasing functional interleukin-1 beta (IL-1β) and interleukin-18 (IL-18). These cytokines play a central role in shaping immune response to pathogens. In this review, we will focus on the mechanisms of inflammasome activation, as well as their role in development of Th1, Th2, and Th17 lymphocytes. The contribution of cytokines IL-1β, IL-18, and IL-33, products of activated inflammasomes, are summarized. Additionally, the role of cytokines released from tissue cells in promoting differentiation of lymphocyte populations is discussed.

Keywords: Th1; Th17; Th2; immune response; inflammasome.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Schematic presentation of the inflammasome structure and pathogen-associated molecular patterns (PAMPs) ligands. NLRP1-CARD binds to and forms a dimer with CARD of pro-caspase-1. NLRP3-CARD-PYD polymerizes with adaptor ASC (PYD-CARD). This is followed by CARD dimerization with CARD-pro-caspase-1. NLRC4-CARD forms a dimer with CARD of ASC (PYD-CARD) adaptor. The PYD of ASC then polymerizes with PYD of the second ASC adaptor molecule. This second ASC CARD binds to CARD of pro-caspase-1. AIM2-PYD dimerizes with PYD of ASC (PYD-CARD), followed by CARD of ASC binding to CARD-pro-caspase-1.
Figure 2
Figure 2
Inflammasome assembly. NLRP3 is used as an example to demonstrate inflammasome assembly. NALRP3 PYD-CARD polymerizes with PYD-CARD of an ASC adaptor. The adaptor CARD then forms a dimer with CARD of pro-caspase-1. The macromolecule formed by oligomerized NLRP3-ASC-pro-caspase-1 complex is assembled into the multi-subunit, wheel-shaped inflammasome complex, which releases active Cas1.
Figure 3
Figure 3
The role of the inflammasome in the differentiation of Th1 lymphocytes. Inflammasome products IL-1β and IL-18 can bind to IL-1R and support the commitment of Th1 lymphocytes by inducing the release of IFN-γ. IFN-γ and IL-12 produced by tissue cells also promotes activation and differentiation of CD4+ lymphocytes to Th1 cells.
Figure 4
Figure 4
The role of the inflammasome in the differentiation of Th2 lymphocytes. The inflammasome produces IL-33 which can promote Th2 differentiation. Another inflammasome product, IL-18, can also promote Th2 lymphocytes development only in the absence of IL-12. Additionally, Th2 differentiation is promoted by tissue released IL-4 and IL-10, which blocks IL-1β activity.
Figure 5
Figure 5
Inflammasome contribute to differentiation of Th17. IL-1β produced by the inflammasome, when combined with TGF-β, IL-6, IL-21, and IL-23 produced by tissue cells, can promote the differentiation of Th17 lymphocytes.
Figure 6
Figure 6
The inflammasome role in the differentiation of naïve CD4 lymphocytes to Th1, Th2, and Th17 cells. Inflammasome products, IL-1β, IL-18, and IL-33, contribute to differentiation of Th1, Th2, and Th17 lymphocytes. However, the lymphocyte commitments and differentiation require additional cytokines, which are released by local tissues.
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