IL-33 promotes innate lymphoid cell-dependent IFN-γ production required for innate immunity to Toxoplasma gondii.
IL-33 promotes innate lymphoid cell-dependent IFN-γ production required for innate immunity to Toxoplasma gondii.
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DOI：
10.7554/elife.65614
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发表时间：
2021-04-30
期刊：
影响因子：
7.7
通讯作者：
Hunter CA
中科院分区：
文献类型：
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作者：
Clark JT;Christian DA;Gullicksrud JA;Perry JA;Park J;Jacquet M;Tarrant JC;Radaelli E;Silver J;Hunter CA
IL-33是抵抗弓形虫寄生虫所需的警报蛋白，但其在对弓形虫的先天抗性中的作用尚不清楚。弓形虫感染可促进间质细胞IL-33表达的增加，并且寄生虫复制水平与受感染组织中IL-33的释放相关。在对感染的反应中，出现了由IL-33R+ NK细胞和ILC1s组成的先天淋巴样细胞（ILC）亚群。在Rag1−/−小鼠中，NK细胞和IFN-γ的ILC1产生介导了对弓形虫的先天抗性，IL-33R的缺失导致ILC应答降低和寄生虫复制增加。此外，给Rag1−/−小鼠注射IL-33可显著降低寄生虫负担，增加IFN-γ的产生，以及与寄生虫控制相关的炎症单核细胞的募集和扩增。外源性IL-33的这些保护作用依赖于内源性IL-12p40和IL-33促进IFN-γ产生ILC的能力。这些结果表明，IL-33与IL-12协同作用可促进il - c介导的对弓形虫的抗性。
IL-33 is an alarmin required for resistance to the parasite Toxoplasma gondii, but its role in innate resistance to this organism is unclear. Infection with T. gondii promotes increased stromal cell expression of IL-33, and levels of parasite replication correlate with release of IL-33 in affected tissues. In response to infection, a subset of innate lymphoid cells (ILC) emerges composed of IL-33R+ NK cells and ILC1s. In Rag1−/−mice, where NK cells and ILC1 production of IFN-γ mediate innate resistance to T. gondii, the loss of the IL-33R resulted in reduced ILC responses and increased parasite replication. Furthermore, administration of IL-33 to Rag1−/− mice resulted in a marked decrease in parasite burden, increased production of IFN-γ, and the recruitment and expansion of inflammatory monocytes associated with parasite control. These protective effects of exogenous IL-33 were dependent on endogenous IL-12p40 and the ability of IL-33 to enhance ILC production of IFN-γ. These results highlight that IL-33 synergizes with IL-12 to promote ILC-mediated resistance to T. gondii.