title: Border Patrol Gone Awry: Lung NKT Cell Activation by Francisella tularensis Exacerbates Tularemia-Like Disease.
abstract: The respiratory mucosa is a major site for pathogen invasion and, hence, a site requiring constant immune surveillance. The type I, semi-invariant natural killer T (NKT) cells are enriched within the lung vasculature. Despite optimal positioning, the role of NKT cells in respiratory infectious diseases remains poorly understood. Hence, we assessed their function in a murine model of pulmonary tularemia--because tularemia is a sepsis-like proinflammatory disease and NKT cells are known to control the cellular and humoral responses underlying sepsis. Here we show for the first time that respiratory infection with Francisella tularensis live vaccine strain resulted in rapid accumulation of NKT cells within the lung interstitium. Activated NKT cells produced interferon-γ and promoted both local and systemic proinflammatory responses. Consistent with these results, NKT cell-deficient mice showed reduced inflammatory cytokine and chemokine response yet they survived the infection better than their wild type counterparts. Strikingly, NKT cell-deficient mice had increased lymphocytic infiltration in the lungs that organized into tertiary lymphoid structures resembling induced bronchus-associated lymphoid tissue (iBALT) at the peak of infection. Thus, NKT cell activation by F. tularensis infection hampers iBALT formation and promotes a systemic proinflammatory response, which exacerbates severe pulmonary tularemia-like disease in mice.
authors.affiliation: Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Hill
authors.affiliation: Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America; Veterans Administration Tennessee Valley Healthcare System, Nashville, Tennessee, United States of America.
authors.forename: Pavlo
authors.initials: P
authors.lastname: Gilchuk
authors.affiliation: Department of Immunology, University of Connecticut Health Center, Farmington, Connecticut, United States of America.
authors.forename: Basak B
authors.initials: BB
authors.lastname: Cicek
authors.affiliation: Department of Psychology and Human Development, Vanderbilt University, Nashville, Tennessee, United States of America.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Osina
authors.affiliation: Veterans Administration Tennessee Valley Healthcare System, Nashville, Tennessee, United States of America.
authors.forename: Kelli L
authors.initials: KL
authors.lastname: Boyd
authors.affiliation: Center for Immunology and Microbial Disease, Albany Medical College, Albany, New York, United States of America.
authors.forename: Douglas M
authors.initials: DM
authors.lastname: Durrant
authors.affiliation: Center for Immunology and Microbial Disease, Albany Medical College, Albany, New York, United States of America.
authors.forename: Dennis W
authors.initials: DW
authors.lastname: Metzger
authors.affiliation: Department of Immunology, University of Connecticut Health Center, Farmington, Connecticut, United States of America.
authors.forename: Kamal M
authors.initials: KM
authors.lastname: Khanna
authors.affiliation: Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America; Veterans Administration Tennessee Valley Healthcare System, Nashville, Tennessee, United States of America.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Joyce
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D005604:Francisella tularensis / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D055611:Natural Killer T-Cells / Q000276:immunology*; D020545:Respiratory Mucosa / Q000276:immunology*; D014406:Tularemia / Q000276:immunology*