title: Microbiota-driven immune cellular maturation is essential for antibody-mediated adaptive immunity to Staphylococcus aureus infection in the eye.
abstract: As an immune-privileged site, the eye, and particularly the outer corneal surface, lacks resident mature immune effector cells. Physical barriers and innate mediators are the best-described effectors of immunity in the cornea. When the barriers are breached, infection can result in rapid tissue destruction, leading to loss of visual acuity and frank blindness. To determine the cellular and molecular components needed for effective adaptive immunity on the corneal surface, we investigated which immune system effectors were required for protection against Staphylococcus aureus corneal infections in mice, which are a serious cause of human eye infections. Both systemically injected and topically applied antibodies to the conserved cell surface polysaccharide poly-N-acetylglucosamine (PNAG) were effective at mediating reductions in corneal pathology and bacterial levels. Additional host factors impacting protection included intercellular adhesion molecule 1 (ICAM-1)-dependent polymorphonuclear leukocyte (PMN) recruitment, functional CD4(+) T cells, signaling via the interleukin-17 (IL-17) receptor, and IL-22 production. In germfree mice, there was no protective efficacy of antibody to PNAG due to the lack of LY6G(+) inflammatory cell coeffector recruitment to the cornea. Protection was manifest after 3 weeks of exposure to conventional mice and acquisition of a resident microbiota. We conclude that in the anterior eye, ICAM-1-mediated PMN recruitment to the infected cornea along with endogenous microbiota-matured CD4(+) T cells producing both IL-17 and IL-22 is required for antibody to PNAG to protect against S. aureus infection.
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Tanweer
authors.initials: T
authors.lastname: Zaidi
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Tauqeer
authors.initials: T
authors.lastname: Zaidi
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Colette
authors.initials: C
authors.lastname: Cywes-Bentley
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Roger
authors.initials: R
authors.lastname: Lu
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA Divisions of Critical Care Medicine (Department of Anesthesiology, Perioperative and Pain Medicine) and Infectious Diseases (Department of Medicine), Boston Children's Hospital, Boston, Massachusetts, USA.
authors.forename: Gregory P
authors.initials: GP
authors.lastname: Priebe
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA gpier@channing.harvard.edu.
authors.forename: Gerald B
authors.initials: GB
authors.lastname: Pier
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology*; D058491:Bacterial Load; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003315:Cornea / Q000382:microbiology / Q000473:pathology; D004195:Disease Models, Animal; D005123:Eye / Q000276:immunology*; D015817:Eye Infections / Q000276:immunology* / Q000382:microbiology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology; D020381:Interleukin-17 / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D064307:Microbiota / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology; D013203:Staphylococcal Infections / Q000276:immunology*; D013211:Staphylococcus aureus / Q000276:immunology*; D000097043:Interleukin-22
chemical_list: D000907:Antibodies, Bacterial; D018799:Intercellular Adhesion Molecule-1; D020381:Interleukin-17; D007378:Interleukins; D000097043:Interleukin-22