Role of NK cells in host defense against pulmonary type A Francisella tularensis infection |
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| Affiliation: | 1. Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, W1157 BSTWR, 200 Lothrop St., Pittsburgh, PA 15261, USA;2. Department of Natural Sciences and Mathematics, West Liberty University, West Liberty, WV 26074, USA;3. Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA;4. Department of Medicine, Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA;5. Center for Vaccine Research, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA;1. Genetic Epidemiology, University of Leicester, UK;2. Sociology & Social Policy, University of Nottingham, UK;1. Department of Oral Pathology and Microbiology, Manipal College of Dental Sciences, Light House Hill Road, Manipal University, Mangalore, Karnataka, India;2. TCR Multispecialty Hospital, Krishnagiri, Tamilnadu, India;1. Department of Surgery, Chonbuk National University Medical School, Jeonju, Republic of Korea;2. Department of Preventive Medicine, Chonbuk National University Medical School, Jeonju, Republic of Korea;3. Department of Internal Medicine, Chonbuk National University Medical School, Jeonju, Republic of Korea;1. Département d’anesthésie-réanimation 2, hôpital Pontchaillou, CHU de Rennes, 2, rue Henri-Le-Guilloux, 35033 Rennes cedex, France;2. Département d’anesthésie-réanimation chirurgicale, hôpital du Bocage, CHU Dijon, avenue de la Côte-de-Nacre, 14033 Caen cedex, France;3. Département de réanimation médicale, hôpital Saint-Antoine, AP–HP, 184, rue du Faubourg-Saint-Antoine, 75571 Paris cedex 12, France;4. Département de réanimation médicochirurgicale, hôpital Saint-Roch, CHU Nice 5, rue Pierre-Devoluy, BP 319, 06006 Nice cedex 1, France;5. Servie d’anesthésie-réanimation, hôpital Pierre-Wertheimer, CHU de Lyon, 29, boulevard Pinel, 69000 Lyon, France;6. Département d’anesthésie-réanimation, hôpital Nord, CHU de Marseille, chemin des Bourrely, 13915 Marseille cedex 20, France;7. Département de réanimation chirurgicale, hôpital Caremeau, CHU de Nîmes, place du Pr.-Debré, 30029 Nîmes cedex 09, France;8. Département d’anesthésie-réanimation, hôpital Necker, AP–HP Paris, 149, rue de Sèvres, 75743 Paris cedex 13, France;9. Département de réanimation-déchocage, CHU de Grenoble, BP 217, 38043 Grenoble cedex, France;10. Service d’anesthésie-réanimation 1, hôpital Pellegrin, CHU de Bordeaux, place Amélie-Raba-Léon, 33076 Bordeaux cedex, France;2. The Center for Health Research, Kaiser Permanente Northwest, Portland, Oregon;3. Division of Research, Kaiser Permanente Northern California, Oakland, California;4. The Group Health Research Institute, Seattle, Washington;6. Fred Hutchinson Cancer Research Center, Seattle, Washington;5. Department of Oncology, Kaiser Permanente Colorado, Denver, Colorado;1. Beijing Center for Disease Control and Prevention, Beijing, PR China;2. ChaoYang District Center for Disease Control and Prevention, Beijing, PR China;3. ChangPing District Center for Disease Control and Prevention, Beijing, PR China;4. TongZhou District Center for Disease Control and Prevention, Beijing, PR China |
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| Abstract: | Pneumonic tularemia is a potentially fatal disease caused by the Category A bioterrorism agent Francisella tularensis. Understanding the pulmonary immune response to this bacterium is necessary for developing effective vaccines and therapeutics. In this study, characterization of immune cell populations in the lungs of mice infected with the type A strain Schu S4 revealed a significant loss in natural killer (NK) cells over time. Since this decline in NK cells correlated with morbidity and mortality, we hypothesized these cells contribute to host defense against Schu S4 infection. Depletion of NK cells prior to Schu S4 challenge significantly reduced IFN-γ and granzyme B in the lung but had no effect on bacterial burden or disease progression. Conversely, increasing NK cell numbers with the anti-apoptotic cytokine IL-15 and soluble receptor IL-15Rα had no significant impact on Schu S4 growth in vivo. A modest decrease in median time to death, however, was observed in live vaccine strain (LVS)-vaccinated mice depleted of NK1.1+ cells and challenged with Schu S4. Therefore, NK cells do not appear to contribute to host defense against acute respiratory infection with type A F. tularensis in vivo, but they play a minor role in protection elicited by LVS vaccination. |
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