TABLE 2

Associations of the IL-33/ST2 axis with bacterial diseases

Disease or pathogenSpecies involvedPrincipal findingsReference
Septic shockMouseTolerance to bacterial LPS is induced by inhibiting the TLR4 pathway via blockade of IL-1R and MyD88 by ST244
MouseOverexpression of ST2 occurs in response to pretreatment with a TLR2 agonist in a model of septic peritonitis47
MouseST2 represses the TLR2 pathway in a dose-dependent manner in BLP-stimulated macrophages; ST2-deficient mice primed with a sublethal dose of BLP showed improved survival against lethal BLP challenge48
MouseIL-33 prevents TLR4-mediated downregulation of CXCR2 expression in neutrophils and their chemotaxis; IL-33 treatment facilitates influx of neutrophils and prevents sepsis induced by cecal ligation and puncture49
MouseST2-deficient mice are more susceptible to septic shock due to inefficient phagosome maturation, decreased NOX2, and free radical production18
HumanElevated plasma concentration of sST2 in sepsis patients vs healthy controls following trauma or abdominal surgery54
HumanIncreased sST2 correlates with severity of disease and mortality after sepsis in humans55
KeratitisMouseBlocking ST2 in mice leads to increased corneal bacterial (P. aeruginosa) changes associated with overexpression of proinflammatory and Th1 cytokines53
MouseDecrease in bacterium-induced changes (P. aeruginosa) in response to rIL-33 treatment in mice is associated with polarization of M2 macrophages and Th2-mediated immune response17
LeptospirosisHumanCirculating sST2 in patients is correlated with hemorrhage and mortality during severe leptospirosis56
TuberculosisMouseNo evident difference in bacterium-induced pulmonary changes found between wild-type and ST2−/− mice despite modest induction of Th1 polarization in ST2−/− mice58
Skin infectionMouseUpregulation of IL-33 mRNA and protein during cutaneous infection with methicillin-resistant S. aureus; injection of rIL-33 prevents S. aureus colonization and accelerates cutaneous wound healing52
HumanExpression of IL-33 was increased in skin of S. aureus-infected patients compared to healthy controls51