The potential role and regulatory mechanism of IL-33/ST2 axis on T lymphocytes during lipopolysaccharide stimulation or perinatal Listeria infection.

BACKGROUND

Interleukin-33 (IL-33) is a member of the interleukin-1 family, which is reported to be important across a range of diseases. However, the mechanisms underlying IL-33/ST2 axis in infectious diseases have not yet been fully addressed.

METHODS

We established both lipopolysaccharide (LPS)-induced injuryin T cells and Listeria monocytogenes (Lm) infection model to determine the effect of IL-33 on infectious immunity.

RESULTS

The T cell proliferation was inhibited by LPS while IL-33 could reverse the outcome. Further, apoptosis was significantly promoted after serum stimulation (ST)2 knockdown, suggesting IL-33, acting through its receptor ST2, may attenuate the inhibitory effect of LPS on T cells through the apoptotic signaling pathway. In this study, we also identified an IL-33-mediated mechanism of T cell differentiation in pregnant mice infected with Lm. Here, we observed the elevated expression of IL-33 in pregnant mice infected with Lm. Furthermore, we revealed that blocking IL-33 markedly decreased the abortion rate and placental bacterial load, but weakened placental inflammatory repair, by inhibiting Th2 cell-mediated immune responses and relatively intensifying Th1-dominent immunoreaction.

CONCLUSIONS

These findings reveal a previously unidentified mechanism underlying IL-33/ST2 axis. IL-33 signaling and targeting T cell-mediated immunity may present a new therapeutic strategy for the treatment of infectious diseases.