Wroblewska Joanna A, Zhang Yuan, Tang Haidong, Guo Xiaohuan, Nagler Cathryn, Fu Yang-Xin
Committee on Immunology, University of Chicago, Chicago, IL 60637.
Department of Pathology, University of Chicago, Chicago, IL 60637.
J Immunol. 2017 Jan 1;198(1):55-60. doi: 10.4049/jimmunol.1600867. Epub 2016 Dec 2.
The immunological components that control resolution of Salmonella infection and successful vaccination are poorly defined. In a model of chronic gastrointestinal infection, we observed that the lymphotoxin (LT) pathway is essential for the clearance and resolution of primary infection of attenuated Salmonella enterica Typhimurium strain SL3261 ΔaroA Using gnotobiotic mice, we show that LTβ receptor (LTβR) signaling and the microbiota are required to promote clearance of attenuated S. enterica Typhimurium from the gut lumen. We also found that LTβR signaling was required for successful immunization and subsequent protection upon challenge with a virulent strain of S enterica Typhimurium. LTβR signaling promoted the development of specific IgG recognizing S enterica Typhimurium during infection, as well as Ag-driven IFN-γ responses. B cell- and type 3 innate lymphoid cell-derived LT signaling, but not T cell-derived LT, contributes to anti-S enterica Typhimurium protective responses. Collectively, our results suggest that LT signaling is essential for multiple steps of anti-S enterica Typhimurium immune responses.
控制沙门氏菌感染消退和成功接种疫苗的免疫成分目前尚不清楚。在慢性胃肠道感染模型中，我们观察到，在使用无菌小鼠的情况下，淋巴毒素（LT）途径对于减毒肠炎沙门氏菌鼠伤寒菌株SL3261ΔaroA原发性感染的清除和消退至关重要。我们发现，需要LTβ受体（LTβR）信号传导和微生物群来促进减毒鼠伤寒沙门氏菌从肠腔的清除。我们还发现，成功免疫以及随后在用毒力强的鼠伤寒沙门氏菌菌株攻击时获得保护需要LTβR信号传导。LTβR信号传导在感染期间促进了识别鼠伤寒沙门氏菌的特异性IgG的产生，以及抗原驱动的IFN-γ反应。B细胞和3型固有淋巴细胞衍生的LT信号传导，而不是T细胞衍生的LT，有助于抗鼠伤寒沙门氏菌的保护性反应。总体而言，我们的结果表明，LT信号传导对于抗鼠伤寒沙门氏菌免疫反应的多个步骤至关重要。
