Citrobacter rodentium Infection Induces Persistent Molecular Changes and Interferon Gamma-Dependent Major Histocompatibility Complex Class II Expression in the Colonic Epithelium.
Citrobacter rodentium Infection Induces Persistent Molecular Changes and Interferon Gamma-Dependent Major Histocompatibility Complex Class II Expression in the Colonic Epithelium.
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DOI：
10.1128/mbio.03233-21
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发表时间：
2021-02-22
期刊：
影响因子：
6.4
通讯作者：
Frankel G
中科院分区：
文献类型：
--
作者：
Mullineaux-Sanders C;Kozik Z;Sanchez-Garrido J;Hopkins EGD;Choudhary JS;Frankel G
大多数关于粘膜表面感染的研究都集中在疾病的急性期。因此，对支持组织恢复和感染后长期后果的分子过程知之甚少。在这里，我们进行了时间深度定量蛋白质组学分析的结肠肠上皮细胞（cIEC）从小鼠感染的天然小鼠病原体啮齿柠檬酸杆菌在对应的时间点的稳态后期（感染后10天[DPI]），清除阶段（13至20 DPI），和4周后的病原体已被清除（48 DPI）。C.依赖III型分泌系统进行感染的啮齿动物用于模拟肠致病性和肠出血性大肠杆菌的感染。我们观察到在感染的清除阶段炎症信号和营养免疫反应的强烈上调。尽管组织形态恢复，但在48 DPI时嗜铬粒蛋白B（Chg B）阳性内分泌细胞仍显著低于基线水平。相反，我们观察到病原体清除后4周参与抗原加工和呈递的蛋白质丰度增加。特别是，长期变化的特征是持续的干扰素γ（IFN-γ）反应和主要组织相容性复合物II类（MHCII）分子在60%的EpCAM+ cIEC中的表达，这在Ifnγ−/−小鼠中没有观察到。尽管如此，野生型和Ifnγ−/−小鼠对C.提示cIEC MHCII对C.啮齿动物。
Most studies of infections at mucosal surfaces have focused on the acute phase of the disease. Consequently, little is known about the molecular processes that underpin tissue recovery and the long-term consequences postinfection. Here, we conducted temporal deep quantitative proteomic analysis of colonic intestinal epithelial cells (cIECs) from mice infected with the natural mouse pathogen Citrobacter rodentium over time points corresponding to the late steady-state phase (10 days postinfection [DPI]), the clearance phase (13 to 20 DPI), and 4 weeks after the pathogen has been cleared (48 DPI). C. rodentium, which relies on a type III secretion system to infect, is used to model infections with enteropathogenic and enterohemorrhagic Escherichia coli. We observe a strong upregulation of inflammatory signaling and nutritional immunity responses during the clearance phase of the infection. Despite morphological tissue recovery, chromogranin B (ChgB)-positive endocrine cells remained significantly below baseline levels at 48 DPI. In contrast, we observed an increased abundance of proteins involved in antigen processing and presentation 4 weeks after pathogen clearance. In particular, long-term changes were characterized by a persistent interferon gamma (IFN-γ) response and the expression of major histocompatibility complex class II (MHCII) molecules in 60% of the EpCAM+ cIECs, which were not seen in Ifnγ−/− mice. Nonetheless, both wild-type and Ifnγ−/− mice mounted similar systemic and colonic IgG responses to C. rodentium and were equally protected from rechallenge, suggesting that cIEC MHCII is not necessary for protective immunity against C. rodentium.
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影响因子：
16.6
作者：
McElrath C;Espinosa V;Lin JD;Peng J;Sridhar R;Dutta O;Tseng HC;Smirnov SV;Risman H;Sandoval MJ;Davra V;Chang YJ;Pollack BP;Birge RB;Galan M;Rivera A;Durbin JE;Kotenko SV
通讯作者：
Kotenko SV
影响因子：
28.3
作者：
Martin PK;Marchiando A;Xu R;Rudensky E;Yeung F;Schuster SL;Kernbauer E;Cadwell K
通讯作者：
Cadwell K
影响因子：
6.4
作者：
Heuberger C;Pott J;Maloy KJ
通讯作者：
Maloy KJ
影响因子：
8
作者：
Cho H;Jaime H;de Oliveira RP;Kang B;Spolski R;Vaziri T;Myers TG;Thovarai V;Shen Z;Fox JG;Leonard WJ;Kelsall BL
通讯作者：
Kelsall BL
影响因子：
3.1
作者：
Chan, Justin M.;Bhinder, Ganive;Vallance, Bruce A.
通讯作者：
Vallance, Bruce A.