Evolutionary loss of inflammasomes in the Carnivora and implications for the carriage of zoonotic infections.
Evolutionary loss of inflammasomes in the Carnivora and implications for the carriage of zoonotic infections.
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DOI：
10.1016/j.celrep.2021.109614
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发表时间：
2021-08-24
期刊：
影响因子：
8.8
通讯作者：
Bryant CE
中科院分区：
文献类型：
--
作者：
Digby Z;Tourlomousis P;Rooney J;Boyle JP;Bibo-Verdugo B;Pickering RJ;Webster SJ;Monie TP;Hopkins LJ;Kayagaki N;Salvesen GS;Warming S;Weinert L;Bryant CE
人畜共患病原体，如COVID-19，在跨越物种感染人类之前，先存在于动物宿主体内。像水貂一样，食肉动物携带许多人畜共患病，然而不同物种宿主免疫基因的多样性如何影响病原体携带尚不清楚。在这里，我们描述了食肉动物病原体感应炎性体途径的渐进式进化下调。这包括核苷酸寡聚结构域亮氨酸富重复受体（NLRs）的缺失，独特的caspase-1/-4效应融合蛋白的获得，该融合蛋白处理gasdermin D孔形成而不诱导快速裂解细胞死亡，以及含有caspase-8的炎性体的形成，该炎性体不能有效地处理白介素-1β。炎性小体调节肠道免疫，但食肉性饮食具有抗菌特性，可以弥补这些免疫途径的损失。我们推测，系统性炎症小体下调的后果，然而，可以损害宿主对特定病原体的感知，这样它们就可以在食肉动物中不被发现。食肉动物缺乏关键的nlr，表达一种独特的caspase-1/-4杂交蛋白，这种蛋白在介导常见炎性体途径的激活方面存在缺陷，很少的活性是由caspase-8驱动的，而不是由caspase-1/-4驱动的。食肉目的物种进化获得了一种独特的caspase-1/-4杂交蛋白的表达。Digby等人表明，该蛋白是NLRP3-和caspase-4依赖性炎性体激活的不良介质。这种炎症小体途径的下调可能损害病原体检测并促进人畜共患感染的传播。
Zoonotic pathogens, such as COVID-19, reside in animal hosts before jumping species to infect humans. The Carnivora, like mink, carry many zoonoses, yet how diversity in host immune genes across species affect pathogen carriage is poorly understood. Here, we describe a progressive evolutionary downregulation of pathogen-sensing inflammasome pathways in Carnivora. This includes the loss of nucleotide-oligomerization domain leucine-rich repeat receptors (NLRs), acquisition of a unique caspase-1/-4 effector fusion protein that processes gasdermin D pore formation without inducing rapid lytic cell death, and the formation of a caspase-8 containing inflammasome that inefficiently processes interleukin-1β. Inflammasomes regulate gut immunity, but the carnivorous diet has antimicrobial properties that could compensate for the loss of these immune pathways. We speculate that the consequences of systemic inflammasome downregulation, however, can impair host sensing of specific pathogens such that they can reside undetected in the Carnivora. Carnivorans lack key NLRs and express a unique caspase-1/-4 hybrid protein This protein is defective in mediating activation of common inflammasome pathways What little activity occurs is driven by caspase-8, rather than caspase-1/-4 Species of the order Carnivora have evolutionarily acquired the expression of a unique caspase-1/-4 hybrid protein. Digby et al. show that this protein is a poor mediator of NLRP3- and caspase-4-dependent inflammasome activation. This downregulation in inflammasome pathways could impair pathogen detection and facilitate transmission of zoonotic infections.
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影响因子：
48
作者：
Anderson KR;Haeussler M;Watanabe C;Janakiraman V;Lund J;Modrusan Z;Stinson J;Bei Q;Buechler A;Yu C;Thamminana SR;Tam L;Sowick MA;Alcantar T;O'Neil N;Li J;Ta L;Lima L;Roose-Girma M;Rairdan X;Durinck S;Warming S
通讯作者：
Warming S
影响因子：
7.7
作者：
Mitchell PS;Roncaioli JL;Turcotte EA;Goers L;Chavez RA;Lee AY;Lesser CF;Rauch I;Vance RE
通讯作者：
Vance RE
形成孔的蛋白质加油D可以调节白细胞介素-1的巨噬细胞分泌。
影响因子：
32.4
作者：
Evavold CL;Ruan J;Tan Y;Xia S;Wu H;Kagan JC
通讯作者：
Kagan JC
影响因子：
8.7
作者：
Dinarello CA
通讯作者：
Dinarello CA
影响因子：
2.4
作者：
Leonard, E. K.;Pearl, D. L.;Weese, J. S.
通讯作者：
Weese, J. S.