Role of the IL-33/ST2 axis during viral diseases

Disease or pathogenSpecies involvedPrincipal findingsReference(s)
BronchiolitisMouseReduction of inflammation and severity of RSV-induced lung infection by blockage of ST2 receptor28
InfluenzaMouseInduction of IL-33 in pulmonary endothelial cells and alveolar epithelial cells after influenza virus infection29
HumanOverexpression of IL-33 in human epithelial cell line MLE-15 in response to different strains of influenza virus29
MouseProduction of IL-13 by ST2+ auxiliary lymphoid cells in response to IL-33 induced by alveolar macrophages following virus infection30
MouseBlockage of IL-33 results in repression of pulmonary functions and remodeling/repair of tracheal passage due to suppression of innate lymphoid ST2+ cells31
MouseAs a vaccine adjuvant with viral hemagglutinin protein, IL-33 enhanced the production of IgG and IgA protective antibodies and Th1/Th2 cytokines in mice33
Herpes simplex virusMouseIL-33 from keratinocytes induces TNF-α and IL-6 expression in mast cells, leading to a protective immune response34
Coxsackie B virusMouseIL-33 enhances production of IFN-γ and TNF-α by CD8+ T and NK cells and triggers production of IL-4 from mast cells, leading to attenuation of inflammatory pancreatitis35
Lymphocytic choriomeningitis virusMouseEndogenously secreted alarmin IL-33 from necrotic cells favors activation, clonal expansion, and cytotoxic activity of CD8+ ST2+ T lymphocytes36
Dengue feverHumanElevated sST2 levels in serum of patients infected with dengue virus37, 38
HumansST2 levels are associated with disease severity and proinflammatory cytokines38
HumanIL-33 levels are inversely correlated with platelet counts and positively correlated with serum transaminases37
AIDSHumanIncreased serum level of sST2 and decreased IL-33 observed in HIV patients vs healthy controls39
Viral hepatitisHumanElevated serum levels of IL-33 in chronically infected HBV patients; IL-33 decrease after IFN treatment41
HumanElevated serum levels of IL-33 and AST/ALTa are correlated in chronically infected HCV patients, and IL-33 levels were decreased following IFN treatment42
HumanOverexpression of IL-33 in vascular endothelial cells, sinusoidal endothelial cells, and fibroblasts during liver fibrosis in humans infected with HBV/HCV10
MouseIL-33 is overexpressed in hepatocytes during acute hepatitis in mice experimentally infected with MHV343
  • a AST, aspartate transaminase; ALT, alanine aminotransferase.