title: Commensal enteric bacteria lipopolysaccharide impairs host defense against disseminated Candida albicans fungal infection.
abstract: Commensal enteric bacteria maintain systemic immune responsiveness that protects against disseminated or localized infection in extra-intestinal tissues caused by pathogenic microbes. However, as shifts in infection susceptibility after commensal bacteria eradication have primarily been probed using viruses, the broader applicability to other pathogen types remains undefined. In sharp contrast to diminished antiviral immunity, we show commensal bacteria eradication bolsters protection against disseminated Candida albicans fungal infection. Enhanced antifungal immunity reflects more robust systemic expansion of Ly6G(hi)Ly6C(int) neutrophils, and their mobilization into infected tissues among antibiotic-treated compared with commensal bacteria-replete control mice. Reciprocally, depletion of neutrophils from expanded levels or intestinal lipopolysaccharide reconstitution overrides the antifungal protective benefits conferred by commensal bacteria eradication. This discordance in antifungal compared with antiviral immunity highlights intrinsic differences in how commensal bacteria control responsiveness for specific immune cell subsets, because pathogen-specific CD8(+) T cells that protect against viruses were suppressed similarly after C. albicans and influenza A virus infection. Thus, positive calibration of antiviral immunity by commensal bacteria is counterbalanced by restrained activation of other immune components that confer antifungal immunity.
authors.affiliation: 1] Division of Infectious Diseases, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA [2] Medical Scientist Training Program, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
authors.forename: T T
authors.initials: TT
authors.lastname: Jiang
authors.affiliation: Division of Infectious Diseases, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
authors.forename: V
authors.initials: V
authors.lastname: Chaturvedi
authors.affiliation: Division of Infectious Diseases, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Ertelt
authors.affiliation: Division of Infectious Diseases, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
authors.forename: L
authors.initials: L
authors.lastname: Xin
authors.affiliation: Division of Infectious Diseases, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
authors.forename: D R
authors.initials: DR
authors.lastname: Clark
authors.affiliation: Division of Infectious Diseases, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Kinder
authors.affiliation: Division of Infectious Diseases, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
authors.forename: S S
authors.initials: SS
authors.lastname: Way
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology; D000950:Antigens, Ly / Q000378:metabolism; D002176:Candida albicans / Q000276:immunology*; D002177:Candidiasis / Q000276:immunology* / Q000382:microbiology* / Q000473:pathology; D004195:Disease Models, Animal; D060467:Disease Resistance / Q000276:immunology*; D004755:Enterobacteriaceae / Q000187:drug effects / Q000276:immunology*; D054884:Host-Pathogen Interactions / Q000187:drug effects / Q000276:immunology*; D007113:Immunity, Innate; D008070:Lipopolysaccharides / Q000276:immunology*; D051379:Mice; D056265:Microbial Interactions / Q000276:immunology; D020556:Neutrophil Infiltration; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D010641:Phenotype
chemical_list: D000900:Anti-Bacterial Agents; D000950:Antigens, Ly; D008070:Lipopolysaccharides; C494192:Ly-6C antigen, mouse; C480309:Ly6G antigen, mouse