IL-27 LIMITS TYPE 2 IMMUNOPATHOLOGY FOLLOWING PARAINFLUENZA VIRUS INFECTION

Gaia Muallem, Sagie Wagage, Yan Sun, Jonathan H. DeLong, Alex Valenzuela, David A. Christian, Gretchen Harms Pritchard, Qun Fang, Elizabeth L. Buza, Deepika Jain, M. Merle Elloso, Carolina B. López, Christopher A. Hunter

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

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.

Original languageEnglish
Article numbere1006173
JournalPLoS pathogens
Volume13
Issue number1
DOIs
StatePublished - Jan 2017

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