The Dynamic Role of the IL-33/ST2 Axis in Chronic Viral-infections: Alarming and Adjuvanting the Immune Response

•IL-33, a guardian of barriers, acts as an alarmin and as an enhancer of immune responses following injury or infection.•sST2, the IL-33 decoy receptor, is considered as a biomarker for allergies, cardiac conditions and infections.•IL-33 has immunotherapeutic and/or adjuvant potential.

Interleukin 33 (IL-33), a member of the IL-1 family, is constitutively expressed in epithelial and in endothelial cells at barrier sites, acting as a danger signal and adjuvanting the immune response following tissue damage and infection. Originally implicated in allergy, IL-33 is also known to be involved in innate and adaptive immune responses by enhancing natural killer, Th1, and CD4 and CD8 T-cell functions. The nature of the antiviral immune response orchestrated by IL-33 depends on the site of infection, the duration of the disease and the cytokine milieu. In this review, we focus on the distinctive contribution of IL-33 as an anti-infective and proinflammatory cytokine in response to cell death and viral infections. The dynamic role of IL-33 in the acute and chronic phases of infection with HIV, hepatitis B and C viruses, and with CMV is highlighted. This review will also discuss the potential immunotherapeutic and adjuvant roles of IL-33.Search Strategy and Selection CriteriaEnglish language, indexed publications in PubMed were searched using combinations of following key words: “interleukin-33”, “IL-33”, “suppression of tumorigenicity 2”, ST2”, “sST2”, “HIV”, “HBV”, “HCV”, “CMV”, “HPV”, “immunotherapy” and “vaccine”. Except for seminal studies, only articles published between 2010 and 2016 were included.