NDLI: Axl receptor blockade protects from invasive pulmonary aspergillosis in mice.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Shibata, Takehiko Habiel, David M. Coelho, Ana Lucia Hogaboam, Cory M.
Description	Author Affiliation: Shibata T ( Immunology Program, Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109); Habiel DM ( Division of Pulmonary and Critical Care Medicine, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048.); Coelho AL ( Division of Pulmonary and Critical Care Medicine, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048.); Hogaboam CM ( Immunology Program, Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109)
Abstract	Aspergillus fumigatus is a sporulating fungus found ubiquitously in the environment, which is quickly contained in the immunocompetent host but can cause lethal invasive aspergillosis in the immunocompromised host. We have recently demonstrated that Axl (one member of the Tyro3, Axl, Mertk receptor family) is a key regulator of antiviral immune responses in the lung. In this study, we investigated the role of Axl in antifungal immunity in a model of invasive pulmonary aspergillosis (IPA). In this model, Aspergillus fumigatus conidia were administered into the lungs of neutrophil-depleted mice, and the mice were monitored for survival, lung inflammatory response, and fungal clearance. The lethal effect of IPA was significantly reduced in anti-Axl mAb-treated mice compared with IgG control-treated mice. Targeting Axl significantly inhibited pulmonary inflammation, including the expression of IL-1ß, IL-6, TNF- , and chitinase-like proteins in whole lung. Further, anti-Axl mAb treatment significantly increased M1 macrophages that highly expressed inducible NO synthase and decreased M2 macrophages that expressed Arginase 1 and were found in inflammatory zone protein (Fizz1). More importantly, anti-Axl mAb treatment significantly increased the number of IFN-Î³-producing T cells and NK cells compared with the IgG control group during IPA. Together, our results demonstrate that the Axl mAb treatment is protective during invasive aspergillosis in neutropenic mice. Collectively, these data suggest a potential deleterious role for Axl during primary immune responses directed against A. fumigatus and novel therapeutic strategy for IPA.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	7
Volume Number	193
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2014-10-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Antibodies, Monoclonal Pharmacology Aspergillosis, Allergic Bronchopulmonary Prevention & Control Aspergillus Fumigatus Immunology Proto-oncogene Proteins Antagonists & Inhibitors Receptor Protein-tyrosine Kinases Animals Pathology Cytokines Disease Models, Animal Intercellular Signaling Peptides And Proteins Killer Cells, Natural Macrophages, Alveolar Mice Nitric Oxide Synthase Type Ii T-lymphocytes Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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