ReviewHost-Pathogen Interactions

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

See allHide authors and affiliations

Sci. Signal.  15 Aug 2017:
Vol. 10, Issue 492, eaan3589
DOI: 10.1126/scisignal.aan3589

You are currently viewing the abstract.

View Full Text


Cytokines are essential signals that promote immune responses against microorganisms. To establish infections, pathogens have developed strategies to block these signals. The interleukin-1 (IL-1) family comprises seven immune-activating cytokines. Three of these, IL-1α, IL-1β, and IL-18, are known to be inhibited by viruses that cause skin diseases in humans. The physiological functions of the remaining four cytokines in this family, IL-33, IL-36α, IL-36β, and IL-36γ, are poorly understood, yet evidence suggests they could play important roles in immunity against bacteria, fungi, and viruses. Using viruses that target the IL-1 family—herpes simplex, Kaposi’s sarcoma–associated herpesvirus, measles, papilloma, and pox—as examples, this review, with six figures, one table, and 146 citations, discusses the hypothesis that IL-36α, IL-36β, and IL-36γ may have evolved to counteract microbial inhibition of IL-1α, IL-1β, and IL-18.


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-36α, IL-36β and IL-36γ, 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-1α, IL-1β, IL-18, and IL-33. Numerous viruses affecting the skin have developed immune evasion strategies that neutralize IL-1α, IL-1β, 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.

View Full Text