Interleukin-33 promotes Th2 immune responses in infected mice with Schistosoma japonicum

Abstract

IL-33, a new member of the IL-1 cytokine family, is associated with many infectious diseases. IL-33 not only is crucial for induction of Th2 polarized responses, but also is involved in induction of inflammation as a proinflammatory cytokine. Whether IL-33 leads to beneficial or worsening outcomes depends on the immune mechanism underlying the pathogensis of each disease condition. This study was to elucidate the role of IL-33 in schistosomiasis japonica in a mouse model. Our results demonstrated that serum levels of IL-33 from infected mice with Schistosoma japonicum began to rise at 1 week postinfection (pi) and reached a peak in 7 weeks pi, and then remained a plateau for 2 weeks, after which its level gradually decreased until 12 weeks pi. Compared with the infection control, exogenous IL-33 administration could increase a Th2 polarized immune response (evidenced by higher levels of IL-5, IL-10, and IL-13, along with lower level of IFN-γ) at 6 weeks pi. Meanwhile, this Th2 polarization was associated with higher infection intensity and liver immunopathology in infected mice, whereas injection of anti-IL-33 mAb into infected mice induced adverse effects on these above immune parameters and immunopathology. These data suggest that IL-33 might act as an inducer of Th2 polarization and plays a crucial role in immunopathology in murine schistosomiasis japonica.

Potential Therapeutic Aspects of Alarmin Cytokine Interleukin 33 or Its Inhibitors in Various Diseases

“…81 IL-33 enhanced periodontal bone loss in Porphyromonas gingivalis infected mice through up-regulated receptor activator of NF-κB ligand expression in B and T lymphocytes in gingival mucosa, 82 which was abolished in ST2 knockout mice. In parasitic infections, IL-33 sensitized the mice to increased T H 2 response and liver disease caused by Schistosoma japonicum, 83 and antagonizing the IL-33 proved protective. The visceral leishmaniasis by Leishmania donovani was enhanced by IL-33 administration by blocking T H 1 cytokines and liver infiltration of leukocytes.…”

Interleukin (IL)-33 is dispensable for Schistosoma mansoni worm maturation, egg excretion, and the maintenance of egg-induced pathology in intestines of mice

“…IL-33 de ciency does not affect S. mansoni worm maturation, reproduction, and egg excretion Schistosome worms are characterized by their dependence on the host immune system, particularly type 2 immunity, for their maturation, reproduction, and egg excretion (14,17,34,36), pointing to the importance of type 2 immunity in the biology of schistosomes. Because IL-33 is known to induce type 2 immunity independently of IL-4 (37), and that a recent study (25) reported increased S. japonicum worm numbers after injection of exogenous IL-33 into infected mice, we thought that its de ciency might compromise the maturation and reproduction of S. mansoni worms. Thus, we compared the morphology and number of worm pairs between IL-33 −/− and WT mice.…”

“…1e), indicating that IL-33 may be dispensable for the excretion of schistosome eggs. Because several studies reported a pathogenic role for IL-33 in egg-induced liver pathology by an increased number of liver tissue eggs (25,26), we sought to see whether IL-33 de ciency would be associated with a decreased number of eggs in liver tissues of IL-33 −/− compared to WT mice.…”

“…However, the role of ILC2-activating cytokines IL-25, IL-33 and TSLP in schistosomiasis remains less understood. Focusing on the liver pathogenesis during S. japonicum infection, two studies showed that IL-33 contributes to the pathology development via induction of type 2 immune responses in infected mice (25,26). Indeed, studies have shown that IL-33 plays a critical role in the development of liver pathology through ILC2-derived IL-13-induced activation of hepatic stellate cells (HSC) (27) and alternative activation of macrophages (M2) (26).…”

“…Indeed, studies have shown that IL-33 plays a critical role in the development of liver pathology through ILC2-derived IL-13-induced activation of hepatic stellate cells (HSC) (27) and alternative activation of macrophages (M2) (26). Moreover, Yu et al (25) found that injection of exogenous IL-33 into S. japonicum-infected mice led to increased worm burden at the sixth week of infection without affecting their fecundity, suggesting that IL-33 might play a role in the migration and maturation of schistosome worms. Whether endogenous IL-33 plays a role in schistosome maturation and reproduction is not known.…”