The IL-33-ILC2 pathway protects from amebic colitis

Abstract

Entamoeba histolytica is a pathogenic protozoan parasite that causes intestinal colitis, diarrhea, and in some cases, liver abscess. Through transcriptomics analysis, we observed that E. histolytica infection was associated with increased expression of IL-33 mRNA in both the human and murine colon. IL-33, the IL-1 family cytokine, is released after cell injury to alert the immune system of tissue damage during infection. Treatment with recombinant IL-33 protected mice from amebic infection and colonic tissue damage; moreover, blocking IL-33 signaling made mice more susceptible to infection and weight loss. IL-33 limited the recruitment of inflammatory immune cells and decreased the pro-inflammatory cytokine IL-6 in the colon. Type 2 immune responses, which are known to be involved in tissue repair, were upregulated by IL-33 treatment during amebic infection. Interestingly, administration of IL-33 protected RAG2-/- mice but not RAG2-/-γc-/- mice, demonstrating that IL-33 mediated protection occurred in the absence of T or B cells but required the presence of innate lymphoid cells (ILCs). IL-33 induced recruitment of ILC2 but not ILC1 and ILC3 in RAG2-/- mice. Adoptive transfer of ILC2s to RAG2-/-γc-/- mice restored IL-33 mediated protection. These data reveal that the IL-33-ILC2 pathway is an important host defense mechanism against amebic colitis.

Effect of curcumin on regulatory B cells in chronic colitis mice involving TLR/MyD88 signaling pathway

“…After curcumin treatment, it significantly restored the length of colon, reduced colon weight, colon weight index and pathological injury score. Colitis is typically characterized by inflammatory cell infiltration and increased secretion of pro‐inflammatory cytokines TNF‐α, IL‐6, IL‐33, CCL‐2, IL‐1β, TGF‐β1, and decreased secretion of anti‐inflammatory cytokines IL‐4, IL‐10, IL‐13, IgA (X. K. Liu et al, 2020; Long et al, 2022; Nijakowski et al, 2021; Uddin et al, 2022). At the same time, Curcumin reduced the proinflammatory cytokines TNF‐α, IL‐6, IL‐33, CCL‐2, IL‐1β and TGF‐β1, significantly promoted the secretion of IL‐4, IL‐10, IL‐13 and IgA, suggesting that curcumin can effectively treat colitis in mice by restoring the balance of the proinflammatory and anti‐inflammatory factors.…”