Defective phagocyte association during infection of Galleria mellonella with Yersinia pseudotuberculosis is detrimental to both insect host and microbe.
Defective phagocyte association during infection of Galleria mellonella with Yersinia pseudotuberculosis is detrimental to both insect host and microbe.
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DOI：
10.1080/21505594.2021.1878672
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发表时间：
2021-12
期刊：
影响因子：
5.2
通讯作者：
Lim J
中科院分区：
文献类型：
--
作者：
Krachler AM;Sirisaengtaksin N;Monteith P;Paine CET;Coates CJ;Lim J
粘附素促进细菌定殖和侵入宿主组织，被认为是毒力因子，但其对免疫介导的损伤作为发病机制的驱动因素的影响仍不清楚。假结核耶尔森菌编码多价粘附分子（MAM）、哺乳动物细胞进入（MCE）家族蛋白和粘附素。MAM广泛存在于革兰氏阴性细菌中，并使肠道细菌能够定殖上皮组织。它们在细菌与宿主先天免疫系统相互作用中的作用以及对致病性的贡献仍不清楚。在这里，我们调查了如何。假结核MAM有助于大蜡螟昆虫模型感染期间的发病机制。我们证明了Y.假结核MAM是有效的细菌结合和被血细胞（宿主吞噬细胞）摄取所必需的。Y.假结核与昆虫和哺乳动物吞噬细胞的相互作用由细菌和宿主因素决定。MAM的缺失和微生物-吞噬细胞相互作用的缺陷增加了G.梅隆内拉减少吞噬细胞协会也导致增加细菌清除。此外，还发现Y.未能参与吞噬细胞的假结核过度激活体液免疫反应，最显著的是黑色素的产生。尽管清除病原体，过度黑化也增加吞噬细胞死亡和宿主死亡率。我们的研究结果为进一步研究微生物和宿主因素如何整合在一个易于处理的实验系统中驱动发病机制提供了基础。
Adhesins facilitate bacterial colonization and invasion of host tissues and are considered virulence factors, but their impact on immune-mediated damage as a driver of pathogenesis remains unclear. Yersinia pseudotuberculosis encodes for a multivalent adhesion molecule (MAM), a mammalian cell entry (MCE) family protein and adhesin. MAMs are widespread in Gram-negative bacteria and enable enteric bacteria to colonize epithelial tissues. Their role in bacterial interactions with the host innate immune system and contribution to pathogenicity remains unclear. Here, we investigated howY. pseudotuberculosis MAM contributes to pathogenesis during infection of the Galleria mellonella insect model. We show that Y. pseudotuberculosis MAM is required for efficient bacterial binding and uptake by hemocytes, the host phagocytes. Y. pseudotuberculosis interactions with insect and mammalian phagocytes are determined by bacterial and host factors. Loss of MAM, and deficient microbe–phagocyte interaction, increased pathogenesis in G. mellonella. Diminished phagocyte association also led to increased bacterial clearance. Furthermore, Y. pseudotuberculosis that failed to engage phagocytes hyperactivated humoral immune responses, most notably melanin production. Despite clearing the pathogen, excessive melanization also increased phagocyte death and host mortality. Our findings provide a basis for further studies investigating how microbe- and host-factors integrate to drive pathogenesis in a tractable experimental system.
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影响因子：
3.7
作者：
Pisano F;Heine W;Rosenheinrich M;Schweer J;Nuss AM;Dersch P
通讯作者：
Dersch P
影响因子：
5.2
作者：
Browne N;Heelan M;Kavanagh K
通讯作者：
Kavanagh K
影响因子：
4.8
作者：
Krachler, Anne Marie;Orth, Kim
通讯作者：
Orth, Kim
影响因子：
4.6
作者：
Clark, Laura C.;Seipke, Ryan F.;Prieto, Pilar;Willemse, Joost;van Wezel, Gilles P.;Hutchings, Matthew I.;Hoskisson, Paul A.
通讯作者：
Hoskisson, Paul A.
影响因子：
5.3
作者：
Bidla, Gawa;Hauling, Thomas;Theopold, Ulrich
通讯作者：
Theopold, Ulrich