IL-33 Has a Protective Effect Against Perinatal Listeriosis by Regulating Mitophagy of CD8+ T Lymphocytes.

Abstract

Listeriosis is a foodborne disease caused by Listeria monocytogenes (Lm) that usually leads to serious adverse outcomes in pregnant women. Interleukin (IL)-33/serum stimulation (ST)2 axis has an important impact on infectious diseases, but its role in listeriosis is rarely studied. Here, the immunomodulatory effects of IL-33/ST2 axis during perinatal Lm infection were investigated. In our study, the perinatal Lm infection model was constructed by injecting Lm into the tail vein of C57BL/6J mice. IL-33/ST2 axis was blocked by intraperitoneal injection of anti-IL-33Rα/ST2 antibody. In vitro, mouse cytotoxic T lymphocyte cell line (CTLL)-2 cells were activated by using CD3/CD28 antibodies. Perinatal Lm infection caused massive necrosis of liver tissue. Blocking IL-33/ST2 axis in pregnant mice inhibited the infiltration of CD8⁺ T lymphocytes into the site of infection and further aggravated liver damage. We also found that IL-33 promotes mitochondrial autophagy in activated CTLL-2 cells in vitro. Mitochondrial autophagy was beneficial to the clearance of damaged mitochondria and reduced the production of reactive oxygen species. IL-33/ST2 axis affects the immune function of CD8⁺ T lymphocytes by regulating mitophagy, which plays a very important role in the occurrence and development of perinatal Lm infection. Immunomodulation targeting IL-33/ST2 axis may be an effective way to adjuvant treatment of perinatal Lm infection.