Inflammatory monocytes promote granuloma control of Yersinia infection.
Inflammatory monocytes promote granuloma control of Yersinia infection.
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DOI：
10.1038/s41564-023-01338-6
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发表时间：
2023-04
影响因子：
28.3
通讯作者：
Brodsky, Igor E.
中科院分区：
文献类型：
--
作者：
Sorobetea, Daniel;Matsuda, Rina;Peterson, Stefan T.;Grayczyk, James P.;Rao, Indira;Krespan, Elise;Lanza, Matthew;Assenmacher, Charles-Antoine;Mack, Matthias;Beiting, Daniel P.;Radaelli, Enrico;Brodsky, Igor E.
肉芽肿是有组织的免疫细胞聚集形成应答慢性感染或抗原的持久性。细菌病原体假结核耶尔森菌（Yp）阻断先天炎症信号和免疫防御，诱导淋巴组织内富含中性粒细胞的脓肉芽肿。在这里，我们发现Yp也触发小鼠肠粘膜内的脓肉芽肿形成。缺乏循环单核细胞的小鼠不能形成明确的脓肉芽肿，中性粒细胞活化有缺陷，并死于Yp感染。缺乏靶向肌动蛋白聚合以阻断吞噬和活性氧爆发的毒力因子的耶尔森菌不会诱导脓毒肉芽肿，这表明肠道脓毒肉芽肿的形成是对Yp破坏细胞骨架动力学的反应。值得注意的是，在缺乏循环单核细胞的小鼠中，毒力因子YopH的突变恢复了肉芽肿的形成和Yp的控制，这表明单核细胞超越了YopH依赖的先天免疫防御封锁。这项工作揭示了一个未被发现的耶尔森氏菌肠道入侵位点，并定义了肠道肉芽肿形成的宿主和病原体驱动因素。
Granulomas are organized immune cell aggregates formed in response to chronic infection or antigen persistence. The bacterial pathogen Yersinia pseudotuberculosis (Yp) blocks innate inflammatory signaling and immune defense, inducing neutrophil-rich pyogranulomas within lymphoid tissues. Here, we uncover that Yp also triggers pyogranuloma formation within the murine intestinal mucosa. Mice lacking circulating monocytes fail to form defined pyogranulomas, have defects in neutrophil activation, and succumb to Yp infection. Yersinia lacking virulence factors that target actin polymerization to block phagocytosis and reactive oxygen burst do not induce pyogranulomas, indicating that intestinal pyogranulomas form in response to Yp disruption of cytoskeletal dynamics. Notably, mutation of the virulence factor YopH restores pyogranuloma formation and control of Yp in mice lacking circulating monocytes, demonstrating that monocytes override YopH-dependent blockade of innate immune defense. This work reveals an unappreciated site of Yersinia intestinal invasion and defines host and pathogen drivers of intestinal granuloma formation.
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影响因子：
48
作者：
Huber W;Carey VJ;Gentleman R;Anders S;Carlson M;Carvalho BS;Bravo HC;Davis S;Gatto L;Girke T;Gottardo R;Hahne F;Hansen KD;Irizarry RA;Lawrence M;Love MI;MacDonald J;Obenchain V;Oleś AK;Pagès H;Reyes A;Shannon P;Smyth GK;Tenenbaum D;Waldron L;Morgan M
通讯作者：
Morgan M
影响因子：
3.1
作者：
Clark, MA;Hirst, BH;Jepson, MA
通讯作者：
Jepson, MA
影响因子：
5.6
作者：
Lamps, LW;Madhusudhan, KT;Scott, MA
通讯作者：
Scott, MA
影响因子：
15.3
作者：
Barnes, Penelope D.;Bergman, Molly A.;Isberg, Ralph R.
通讯作者：
Isberg, Ralph R.
DOI：
10.1111/j.1365-2257.2004.00599.x
发表时间：
2004-06-01
期刊：
CLINICAL AND LABORATORY HAEMATOLOGY
影响因子：
--
作者：
Latger-Cannard, V;Besson, I;Lecompte, T
通讯作者：
Lecompte, T