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. Treatment with recombinant IL-33 protected mice from amebic infection and intestinal tissue damage; moreover, blocking IL-33 signaling made mice more susceptible to amebiasis. IL-33 limited the recruitment of inflammatory immune cells and decreased the pro-inflammatory cytokine IL-6 in the cecum. Type 2 immune responses 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 required the presence of innate lymphoid cells (ILCs). IL-33 induced recruitment of ILC2 but not ILC1 and ILC3 in RAG2^−/− mice. At baseline and after amebic infection, there was a significantly higher IL13+ILC2s in C57BL/J mice, which are naturally resistant to amebiasis, than CBA/J 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.

溶组织内阿米巴是一种致病性原生动物寄生虫，可引起肠结肠炎、腹泻，在某些情况下还会引起肝脓肿。通过转录组学分析，我们观察到E. histolytica感染与人和小鼠结肠中 IL-33 mRNA 的表达增加有关。IL-33 是 IL-1 家族细胞因子，在细胞损伤后释放，以提醒免疫系统注意组织损伤。用重组 IL-33 治疗可保护小鼠免受阿米巴感染和肠组织损伤；此外，阻断 IL-33 信号使小鼠更容易感染阿米巴病。IL-33 限制了炎症免疫细胞的募集并减少了盲肠中的促炎细胞因子 IL-6。2 型免疫反应在阿米巴感染期间被 IL-33 治疗上调。有趣的是，给予 IL-33 可保护 RAG2 ^{– /–}小鼠，但不能保护 RAG2 ^−/− γc ^−/−小鼠，证明 IL-33 介导的保护需要先天淋巴样细胞 (ILC) 的存在。^{IL-33 在 RAG2 -/-}小鼠中诱导 ILC2 而非 ILC1 和 ILC3 的募集。在基线和阿米巴感染后，天然抗阿米巴病的 C57BL/J 小鼠中的 IL13+ILC2s 显着高于 CBA/J 小鼠。将 ILC2 过继转移至 RAG2 ^-/- γc ^-/-小鼠可恢复 IL-33 介导的保护作用。这些数据表明 IL-33-ILC2 通路是宿主对抗阿米巴结肠炎的重要防御机制。