IL-27 Limits Type 2 Immunopathology Following Parainfluenza Virus Infection

PLoS Pathogens

Jonathan H. DeLong¹  Sagie Wagage²  Elizabeth L. Buza³  Gaia Muallem³  M. Merle Elloso³  David A. Christian³  Alex Valenzuela³  Carolina B. López³  Gretchen Harms Pritchard³  Qun Fang³  Yan Sun³  Deepika Jain³  Christopher A. Hunter⁴ 

[1] Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, United States of America;Department of Nephrology, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America;Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America;Janssen Research & Development, LLC, Immunology Discovery Research, Spring House, Pennsylvania, United States of America

关键词: T cells;    Respiratory infections;    Immune response;    Cloning;    Cytokines;    Flow cytometry;    Inflammation;    Cytopathology;   

DOI  :  10.1371/journal.ppat.1006173

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Respiratory paramyxoviruses are important causes of morbidity and mortality, particularly of infants and the elderly. In humans, a T helper (Th)2-biased immune response to these infections is associated with increased disease severity; however, little is known about the endogenous regulators of these responses that may be manipulated to ameliorate pathology. IL-27, a cytokine that regulates Th2 responses, is produced in the lungs during parainfluenza infection, but its role in disease pathogenesis is unknown. To determine whether IL-27 limits the development of pathogenic Th2 responses during paramyxovirus infection, IL-27-deficient or control mice were infected with the murine parainfluenza virus Sendai virus (SeV). Infected IL-27-deficient mice experienced increased weight loss, more severe lung lesions, and decreased survival compared to controls. IL-27 deficiency led to increased pulmonary eosinophils, alternatively activated macrophages (AAMs), and the emergence of Th2 responses. In control mice, IL-27 induced a population of IFN-γ+/IL-10+ CD4+ T cells that was replaced by IFN-γ+/IL-17+ and IFN-γ+/IL-13+ CD4+ T cells in IL-27-deficient mice. CD4+ T cell depletion in IL-27-deficient mice attenuated weight loss and decreased AAMs. Elimination of STAT6 signaling in IL-27-deficient mice reduced Th2 responses and decreased disease severity. These data indicate that endogenous IL-27 limits pathology during parainfluenza virus infection by regulating the quality of CD4+ T cell responses and therefore may have therapeutic potential in paramyxovirus infections.

【 授权许可】

CC BY