Inflammasomes and Their Role in Innate Immunity of Sexually Transmitted Infections

Abstract

Inflammasomes are multiprotein complexes present in the cytosol as pattern recognition receptors or as sensors of damage-associated molecular patterns. After recognition of microbe-associated molecular patterns or host-derived danger signals, nucleotide oligomerization domain-like receptors oligomerize to form inflammasomes. The activation of inflammasomes results in an alarm, which is raised to alert adjacent cells through the processing and release of a number of other substrates present in the cytosol. A wide array of inflammasomes and their adapter molecules have been identified in the host's innate immune system in response to various pathogens. Components of specific pathogens activate different inflammasomes, which once activated in response to pathogen-induced infection, induce the activation of caspases, and the release of mature forms of interleukin-1β (IL-1β) and IL-18. Identifying the mechanisms underlying pathogen-induced inflammasome activation is important if we are to develop novel therapeutic strategies to target sexually transmitted infections (STIs) related pathogens. This information is currently lacking in literature. In this review, we have discussed the role of various inflammasomes in sensing different STIs, as well as the beneficial or detrimental effects of inflammasome signaling in host resistance. Additionally, we have discussed both canonical and non-canonical processing of IL-1β induced with respect to particular infections. Overall, these findings transform our understanding of both the basic biology and clinical relevance of inflammasomes.

Keywords: NOD-like receptors; host defense; inflammasomes; innate immunity; pathogens; sexually transmitted infections.

Figure 1

Model: inflammasome activation and pro-inflammatory cytokine release during various STIs. Synchronization of various inflammasomes and their adapters in the regulation of pro-inflammatory cytokine release. Cytosolic DNA and viral RNA of various viruses (HIV, HSV-2, and HPV) and different pathogens are sensed by AIM2 inflammasome. PAMPs and DAMPs of Haemophilus ducreyi, Neisseria gonorrhoeae, and TPF1 (Treponema pallidum factor-1) of Treponema pallidum trigger NLRP3 inflammasome. CPAF protease of Chlamydia trachomatis inhibits NF-κB signaling and pathogen triggers NLRP3 signaling via Nod 1 adapter. IL-1β release resulting from Candida albicans infection is mediated by caspase-8 activation. Abbreviations: NLRP, Nod-like receptor protein; NLRC4, Nod-like receptor containing CARD4; AIM2, absent in melanoma 2; IFI16, interferon inducible; LPS, lipopolysaccharide; MDP, muramyl dipeptide; PFTs, pore forming toxins; ROS, reactive oxygen species.