Pneumoviruses infect eosinophils and elicit MyD88-dependent release of chemoattractant cytokines and interleukin-6.
Eosinophils are recruited to the lung in response to infection with pneumovirus pathogens and have been associated with both the pathophysiologic sequelae of infection and, more recently, with accelerated virus clearance. Here, we demonstrate that the pneumovirus pathogens, respiratory syncytial virus (RSV) and pneumonia virus of mice (PVM), can infect human and mouse eosinophils, respectively, and that virus infection of eosinophils elicits the release of disease-related proinflammatory mediators from eosinophils. RSV replication in human eosinophils results in the release of infectious virions and in the release of the proinflammatory mediator, interleukin-6 (IL-6). PVM replication in cultured bone marrow eosinophils (bmEos) likewise results in release of infectious virions and the proinflammatory mediators IL-6, IP-10, CCL2, and CCL3. In contrast to the findings reported in lung tissue of RSV-challenged mice, PVM replication is accelerated in MyD88 gene-deleted bmEos, whereas release of cytokines is diminished. Interestingly, exogenous IL-6 suppresses virus replication in MyD88 gene-deleted bmEos, suggesting a role for a MyD88-dependent cytokine-mediated feedback circuit in modulating this response. Taken together, our findings suggest that eosinophils are targets of virus infection and may have varied and complex contributions to the pathogenesis and resolution of pneumovirus disease.
Dyer
Kimberly D
KD
Eosinophil Biology Section, Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA. kdyer@niaid.nih.gov
Percopo
Caroline M
CM
Fischer
Elizabeth R
ER
Gabryszewski
Stanislaw J
SJ
Rosenberg
Helene F
HF
D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000821:virology; D018925:Chemokines / Q000378:metabolism*; D002630:Chemotactic Factors / Q000378:metabolism; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000821:virology; D015850:Interleukin-6 / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D018111:Pneumovirus / Q000502:physiology*; D018186:Pneumovirus Infections / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D017201:Virus Shedding / Q000187:drug effects / Q000235:genetics / Q000502:physiology
D018925:Chemokines; D002630:Chemotactic Factors; D015850:Interleukin-6; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88