Dual RNA sequencing reveals dendritic cell reprogramming in response to typhoidal Salmonella invasion.
Dual RNA sequencing reveals dendritic cell reprogramming in response to typhoidal Salmonella invasion.
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DOI：
10.1038/s42003-022-03038-z
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发表时间：
2022-02-04
影响因子：
5.9
通讯作者：
Simmons A
中科院分区：
文献类型：
--
作者：
Aulicino A;Antanaviciute A;Frost J;Sousa Geros A;Mellado E;Attar M;Jagielowicz M;Hublitz P;Sinz J;Preciado-Llanes L;Napolitani G;Bowden R;Koohy H;Drakesmith H;Simmons A
肠道沙门氏菌是世界范围内的主要疾病负担。S.伤寒沙门氏菌（S.伤寒（Typhi）是每年影响1090万人的潜在威胁生命的伤寒的原因。虽然非伤寒沙门氏菌（NTS）血清型通常会引发自限性腹泻，但侵袭性NTS菌血症是一个日益严重的公共卫生挑战。树突状细胞（Dendritic cells，DC）是人体免疫系统中重要的专职抗原提呈细胞。病原菌破坏DC功能和阻止T细胞识别的能力有助于它们在宿主内的存活和传播。在这里，我们采用双重RNA测序来确定不同的沙门氏菌致病变种如何与受感染的DC一起重塑其基因表达。我们发现DC利用铁处理途径来防御入侵的沙门氏菌，S。伤寒能够通过对亚硝化压力的强烈反应来规避。与此同时，我们发现了侵入性NTS用于损害DC功能的替代策略。Aulicino，Antanaviciute等人研究了树突状细胞（DC）中对侵袭性沙门氏菌菌株的转录应答。它们表明S.伤寒对亚硝化应激途径产生反应，并提出铁的吸收和转运在预防感染中的作用，病原体可以绕过它。同时，他们发现侵袭性沙门氏菌采用几种机制，靶向免疫的更经典方面，以损害DC功能。
Salmonella enterica represent a major disease burden worldwide. S. enterica serovar Typhi (S. Typhi) is responsible for potentially life-threatening Typhoid fever affecting 10.9 million people annually. While non-typhoidal Salmonella (NTS) serovars usually trigger self-limiting diarrhoea, invasive NTS bacteraemia is a growing public health challenge. Dendritic cells (DCs) are key professional antigen presenting cells of the human immune system. The ability of pathogenic bacteria to subvert DC functions and prevent T cell recognition contributes to their survival and dissemination within the host. Here, we adapted dual RNA-sequencing to define how different Salmonella pathovariants remodel their gene expression in tandem with that of infected DCs. We find DCs harness iron handling pathways to defend against invading Salmonellas, which S. Typhi is able to circumvent by mounting a robust response to nitrosative stress. In parallel, we uncover the alternative strategies invasive NTS employ to impair DC functions. Aulicino, Antanaviciute et al investigate the transcriptional response to invasive Salmonella strains in dendritic cells (DCs). They show that S. Typhi mount a response against nitrosative stress pathways and propose a role of iron uptake and transport in preventing infection, which the pathogen can bypass. In parallel, they find that invasive Salmonella employs several mechanisms targeting more classic aspects of immunity to impair DC function.
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DOI：
10.1016/j.medj.2020.10.004
发表时间：
2021-02-12
期刊：
Med (New York, N.Y.)
影响因子：
--
作者：
Frost JN;Tan TK;Abbas M;Wideman SK;Bonadonna M;Stoffel NU;Wray K;Kronsteiner B;Smits G;Campagna DR;Duarte TL;Lopes JM;Shah A;Armitage AE;Arezes J;Lim PJ;Preston AE;Ahern D;Teh M;Naylor C;Salio M;Gileadi U;Andrews SC;Dunachie SJ;Zimmermann MB;van der Klis FRM;Cerundolo V;Bannard O;Draper SJ;Townsend ARM;Galy B;Fleming MD;Lewis MC;Drakesmith H
通讯作者：
Drakesmith H
影响因子：
--
作者：
Karolchik, Donna;Hinrichs, Angie S;Kent, W James
通讯作者：
Kent, W James
影响因子：
4.8
作者：
Bang, Iel-Soo;Liu, Limin;Fang, Ferric C.
通讯作者：
Fang, Ferric C.
影响因子：
4.1
作者：
JORDAN, I;KAPLAN, J
通讯作者：
KAPLAN, J
影响因子：
14.9
作者：
Haeussler M;Zweig AS;Tyner C;Speir ML;Rosenbloom KR;Raney BJ;Lee CM;Lee BT;Hinrichs AS;Gonzalez JN;Gibson D;Diekhans M;Clawson H;Casper J;Barber GP;Haussler D;Kuhn RM;Kent WJ
通讯作者：
Kent WJ