Interleukin-36 cytokines may overcome microbial immune evasion strategies that inhibit interleukin-1 family signaling

Abstract

Pathogens deploy immune evasion strategies to successfully establish infections within their hosts. Naturally, the host responds by acquiring mechanisms to counter these strategies. There is increasing evidence that the three interleukin-36 (IL-36) cytokines, IL-36a, IL-36b and IL-36g, play important roles in host immunity. With a focus on the skin as a target for microbial and viral invasion, the current knowledge of IL-36 functions is reviewed. Furthermore, the hypothesis that the IL-36s have evolved to counteract virulence factors is presented using viruses as an example. The IL-36s are related to IL-1a, IL-1b, IL-18, and IL-33. Numerous viruses affecting the skin have developed immune evasion strategies that neutralize IL-1a, IL-1b, or IL-18 signaling or combinations of these pathways. Through small differences in activation mechanisms and receptor utilization, it is possible that IL-36 signaling may proceed unhindered in the presence of these viral inhibitors. Thus, one physiological function of the IL-36s may be to counteract microbial immune evasion.

Plasma protein profiling reflects TH1-driven immune dysregulation in common variable immunodeficiency

“…IL-36B is a poorly understood immune-activating cytokine belonging to the IL-1 family that has been suggested to play an important role in host defense by counteracting microbial immune evasion. 49 Our study has some limitations. The first is the restricted number of patients included, especially with regard to the heterogeneity of the clinical manifestations of CVID.…”

The genetic prehistory of the Andean highlands 7,000 Years BP though European contact

“…The second most highly differentiated SNPs were in the 35 vicinity of RPS29, which codes for a ribosomal protein, and is involved in viral mRNA translation and metabolism, including that of influenza (59). Another top gene, IL-36R (rank #36), is thought to have evolved alternative cytokine signaling to compensate for viruses, such as pox viruses, that can evade the immune system (60). Furthermore, the top SNP associated with IL-36R (rs1117797) exhibits a QTL signal associated with IL18RAP, a gene involved in mediating the immune 40 response to the vaccinia virus (61).…”

New Insights in Candida albicans Innate Immunity at the Mucosa: Toxins, Epithelium, Metabolism, and Beyond

“…Included in the IL-1 cytokine superfamily, IL-36 members are emerging as important mediators of the immune response to microbial infections and inflammatory skin diseases (Jensen, 2017;Buhl and Wenzel, 2019). IL-36 family includes three agonistic cytokines, IL-36α, IL-36β, and IL-36γ, and one antagonistic molecule, IL-36RA, all of them signaling through the dimer composed of IL-36R and IL-1R accessory protein.…”

“…IL-36 family includes three agonistic cytokines, IL-36α, IL-36β, and IL-36γ, and one antagonistic molecule, IL-36RA, all of them signaling through the dimer composed of IL-36R and IL-1R accessory protein. This cytokine family is involved in the activation of myeloid cells (including monocytes and dendritic cells) and epithelial cells, such as skin keratinocytes, contributing to leukocyte recruitment or AMP secretion (Gresnigt and van de Veerdonk, 2013;Jensen, 2017;Bassoy et al, 2018;Swindell et al, 2018).…”

“…However, little is known on the role of IL-36 in mucosal tissues, although an increasing number of studies have shown the relevance of these proteins for the response to a wide variety of stimuli (Jensen, 2017). Importantly, IL-36γ, IL-23, and IL-22 are induced during intestinal mucosa damage, and are essential for tissue repair, host cell survival, and antimicrobial activity (Ngo et al, 2018).…”