title: IL-10 restrains IL-17 to limit lung pathology characteristics following pulmonary infection with Francisella tularensis live vaccine strain.
abstract: IL-10 production during intracellular bacterial infections is generally thought to be detrimental because of its role in suppressing protective T-helper cell 1 (Th1) responses. Francisella tularensis is a facultative intracellular bacterium that activates both Th1 and Th17 protective immune responses. Herein, we report that IL-10-deficient mice (Il10(-/-)), despite having increased Th1 and Th17 responses, exhibit increased mortality after pulmonary infection with F. tularensis live vaccine strain. We demonstrate that the increased mortality observed in Il10(-/-)-infected mice is due to exacerbated IL-17 production that causes increased neutrophil recruitment and associated lung pathology. Thus, although IL-17 is required for protective immunity against pulmonary infection with F. tularensis live vaccine strain, its production is tightly regulated by IL-10 to generate efficient induction of protective immunity without mediating pathology. These data suggest a critical role for IL-10 in maintaining the delicate balance between host immunity and pathology during pulmonary infection with F. tularensis live vaccine strain.
authors.affiliation: Division of Infectious Diseases, Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors.forename: Samantha R
authors.initials: SR
authors.lastname: Slight
authors.affiliation: Division of Infectious Diseases, Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors.forename: Leticia
authors.initials: L
authors.lastname: Monin
authors.affiliation: Division of Infectious Diseases, Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors.forename: Radha
authors.initials: R
authors.lastname: Gopal
authors.affiliation: Division of Infectious Diseases, Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors.forename: Lyndsay
authors.initials: L
authors.lastname: Avery
authors.affiliation: Division of Infectious Diseases, Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors.forename: Marci
authors.initials: M
authors.lastname: Davis
authors.affiliation: Division of Infectious Diseases, Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors.forename: Hillary
authors.initials: H
authors.lastname: Cleveland
authors.affiliation: Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors.forename: Tim D
authors.initials: TD
authors.lastname: Oury
authors.affiliation: Division of Allergy, Immunology and Rheumatology, Department of Medicine, University of Rochester Medical Center, Rochester, New York.
authors.forename: Javier
authors.initials: J
authors.lastname: Rangel-Moreno
authors.affiliation: Division of Infectious Diseases, Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania. Electronic address: shabaana.khader@chp.edu.
authors.forename: Shabaana A
authors.initials: SA
authors.lastname: Khader
mesh_terms: D000818:Animals; D001428:Bacterial Vaccines / Q000276:immunology*; D004198:Disease Susceptibility; D005604:Francisella tularensis / Q000502:physiology*; D007249:Inflammation / Q000473:pathology; D016753:Interleukin-10 / Q000096:biosynthesis / Q000172:deficiency / Q000378:metabolism*; D020381:Interleukin-17 / Q000378:metabolism*; D008168:Lung / Q000276:immunology* / Q000382:microbiology / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D020556:Neutrophil Infiltration; D012141:Respiratory Tract Infections / Q000276:immunology / Q000382:microbiology* / Q000473:pathology / Q000517:prevention & control; D018417:Th1 Cells / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology; D014406:Tularemia / Q000276:immunology / Q000382:microbiology / Q000473:pathology / Q000517:prevention & control
chemical_list: D001428:Bacterial Vaccines; D020381:Interleukin-17; D016753:Interleukin-10