title: Cutting Edge: Lymphotoxin Signaling Is Essential for Clearance of Salmonella from the Gut Lumen and Generation of Anti-Salmonella Protective Immunity.
abstract: 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.
authors.affiliation: Committee on Immunology, University of Chicago, Chicago, IL 60637.
authors.forename: Joanna A
authors.identifier: 0000-0001-5364-7236
authors.initials: JA
authors.lastname: Wroblewska
authors.affiliation: Department of Pathology, University of Chicago, Chicago, IL 60637.
authors.forename: Yuan
authors.identifier: 0000-0003-0022-1201
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pathology, University of Chicago, Chicago, IL 60637.|Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75390; and.
authors.forename: Haidong
authors.identifier: 0000-0002-1512-2655
authors.initials: H
authors.lastname: Tang
authors.affiliation: Tsinghua University School of Medicine, Beijing 100084, China.
authors.forename: Xiaohuan
authors.identifier: 0000-0003-0316-2403
authors.initials: X
authors.lastname: Guo
authors.affiliation: Committee on Immunology, University of Chicago, Chicago, IL 60637.|Department of Pathology, University of Chicago, Chicago, IL 60637.
authors.forename: Cathryn
authors.initials: C
authors.lastname: Nagler
authors.affiliation: Committee on Immunology, University of Chicago, Chicago, IL 60637; yang-xin.fu@utsouthwestern.edu.|Department of Pathology, University of Chicago, Chicago, IL 60637.|Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75390; and.
authors.forename: Yang-Xin
authors.identifier: 0000-0001-8441-6617
authors.initials: YX
authors.lastname: Fu
mesh_terms: D000818:Animals; D004797:Enzyme-Linked Immunosorbent Assay; D000069196:Gastrointestinal Microbiome / Q000276:immunology*; D005856:Germ-Free Life; D008233:Lymphotoxin-alpha / Q000276:immunology*; D051379:Mice; D012481:Salmonella Infections, Animal / Q000276:immunology*; D012486:Salmonella typhimurium / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology
chemical_list: D008233:Lymphotoxin-alpha