Liaoning Key Laboratory of Marine Animal Immunology, Dalian Ocean University, Dalian 116023, China.
Liaoning Key Laboratory of Marine Animal Immunology and Disease Control, Dalian Ocean University, Dalian 116023, China.
J Immunol. 2020 Nov 1;205(9):2402-2413. doi: 10.4049/jimmunol.2000294. Epub 2020 Sep 28.
The long-term evolutionary interaction between the host and symbiotic microbes determines their cooperative relationship. It is well known that the symbiotic microbes have evolved various mechanisms to either benefit or exploit the mammalian host immune system to maintain homeostasis. However, the strategies employed by the symbiotic microbes to overcome host immune responses in invertebrates are still not clear. In the current study, the hemolymph microbes in oyster were found to be able to directly bind an oyster Ig superfamily member (IgSF) (designated as IgIT) to inhibit the immune responses of hemocytes. The mRNA transcripts of IgIT in hemocytes increased significantly after the stimulation with hemolymph microbes. IgIT was found to be located on the hemocyte membrane and it was able to directly bind the hemolymph microbes and polysaccharides via its three Ig domains and recruited the protein tyrosine phosphatase SHP2 through its ITIM. The recruited SHP2 inhibited the activities of ERK, P38 and JNK proteins to reduce the productions of dual oxidase 2 (Duox2) and defensin 2 (Def2), which eventually protected the hemolymph microbes from Duox2/Def2-mediated elimination. Collectively, the results suggest that the oyster IgIT-SHP2 signaling pathway can recognize bacteria capable of residing in oyster hemolymph and inhibit innate immune responses, which contributes to the maintenance, colonization, and survival of hemolymph microbes.
宿主与共生微生物之间的长期进化相互作用决定了它们的合作关系。众所周知，共生微生物已经进化出各种机制，要么受益于哺乳动物宿主的免疫系统，要么利用宿主的免疫系统来维持体内平衡。然而，共生微生物在无脊椎动物中克服宿主免疫反应所采用的策略仍不清楚。在本研究中，发现牡蛎的血淋巴微生物能够直接结合牡蛎 Ig 超家族成员（IgSF）（命名为 IgIT），从而抑制血细胞的免疫反应。血细胞中 IgIT 的 mRNA 转录本在受到血淋巴微生物刺激后显著增加。IgIT 被发现位于血细胞膜上，它能够通过其三个 Ig 结构域直接结合血淋巴微生物和多糖，并通过其 ITIM 募集蛋白酪氨酸磷酸酶 SHP2。募集的 SHP2 抑制 ERK、P38 和 JNK 蛋白的活性，从而减少双氧化酶 2（Duox2）和防御素 2（Def2）的产生，最终使血淋巴微生物免受 Duox2/Def2 介导的消除。总的来说，这些结果表明，牡蛎 IgIT-SHP2 信号通路可以识别能够存在于牡蛎血淋巴中的细菌，并抑制先天免疫反应，有助于血淋巴微生物的维持、定植和存活。
