title: Toll-like receptor-deficient mice reveal how innate immune signaling influences Salmonella virulence strategies.
abstract: Pathogens utilize features of the host response as cues to regulate virulence gene expression. Salmonella enterica serovar Typhimurium (ST) sense Toll-like receptor (TLR)-dependent signals to induce Salmonella Pathogenicity Island 2 (SPI2), a locus required for intracellular replication. To examine pathogenicity in the absence of such cues, we evaluated ST virulence in mice lacking all TLR function (Tlr2(-/-)xTlr4(-/-)xUnc93b1(3d/3d)). When delivered systemically to TLR-deficient mice, ST do not require SPI2 and maintain virulence by replicating extracellularly. In contrast, SPI2 mutant ST are highly attenuated after oral infection of the same mice, revealing a role for SPI2 in the earliest stages of infection, even when intracellular replication is not required. This early requirement for SPI2 is abolished in MyD88(-/-)xTRIF(-/-) mice lacking both TLR- and other MyD88-dependent signaling pathways, a potential consequence of compromised intestinal permeability. These results demonstrate how pathogens use plasticity in virulence strategies to respond to different host immune environments.
authors: Department of Molecular and Cell Biology, Division of Immunology and Pathogenesis, University of California, Berkeley, Berkeley, CA 94720, USA.
authors: Kelsey E
authors: KE
authors: Sivick
authors: Department of Molecular and Cell Biology, Division of Immunology and Pathogenesis, University of California, Berkeley, Berkeley, CA 94720, USA.
authors: Nicholas
authors: N
authors: Arpaia
authors: Department of Molecular and Cell Biology, Division of Immunology and Pathogenesis, University of California, Berkeley, Berkeley, CA 94720, USA.
authors: Gabrielle L
authors: GL
authors: Reiner
authors: Department of Molecular and Cell Biology, Division of Immunology and Pathogenesis, University of California, Berkeley, Berkeley, CA 94720, USA.
authors: Bettina L
authors: BL
authors: Lee
authors: Department of Molecular and Cell Biology, Division of Immunology and Pathogenesis, University of California, Berkeley, Berkeley, CA 94720, USA.
authors: Bethany R
authors: BR
authors: Russell
authors: Department of Molecular and Cell Biology, Division of Immunology and Pathogenesis, University of California, Berkeley, Berkeley, CA 94720, USA. Electronic address: barton@berkeley.edu.
authors: Gregory M
authors: GM
authors: Barton
mesh_terms: D000818:Animals; D054884:Host-Pathogen Interactions; D007113:Immunity, Innate; D051379:Mice; D018345:Mice, Knockout; D012486:Salmonella typhimurium / Q000276:immunology* / Q000472:pathogenicity*; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000172:deficiency / Q000276:immunology*; D014774:Virulence
chemical_list: D051193:Toll-Like Receptors