Induction of high-affinity IgE receptor on lung dendritic cells during viral infection leads to mucous cell metaplasia.
Respiratory viral infections are associated with an increased risk of asthma, but how acute Th1 antiviral immune responses lead to chronic inflammatory Th2 disease remains undefined. We define a novel pathway that links transient viral infection to chronic lung disease with dendritic cell (DC) expression of the high-affinity IgE receptor (FcepsilonRIalpha). In a mouse model of virus-induced chronic lung disease, in which Sendai virus triggered a switch to persistent mucous cell metaplasia and airway hyperreactivity after clearance of replicating virus, we found that FceRIa(-/-) mice no longer developed mucous cell metaplasia. Viral infection induced IgE-independent, type I IFN receptor-dependent expression of FcepsilonRIalpha on mouse lung DCs. Cross-linking DC FcepsilonRIalpha resulted in the production of the T cell chemoattractant CCL28. FceRIa(-/-) mice had decreased CCL28 and recruitment of IL-13-producing CD4(+) T cells to the lung after viral infection. Transfer of wild-type DCs to FceRIa(-/-) mice restored these events, whereas blockade of CCL28 inhibited mucous cell metaplasia. Therefore, lung DC expression of FcepsilonRIalpha is part of the antiviral response that recruits CD4(+) T cells and drives mucous cell metaplasia, thus linking antiviral responses to allergic/asthmatic Th2 responses.
Grayson
Mitchell H
MH
Division of Allergy and Immunology, Department of Internal Medicine, Washington University School of Medicine, Saint Louis, MO 63110, USA. wheeze@allergist.com
Cheung
Dorothy
D
Rohlfing
Michelle M
MM
Kitchens
Robert
R
Spiegel
Daniel E
DE
Tucker
Jennifer
J
Battaile
John T
JT
Alevy
Yael
Y
Yan
Le
L
Agapov
Eugene
E
Kim
Edy Y
EY
Holtzman
Michael J
MJ
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000821:virology; D018929:Cell Culture Techniques; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology / Q000821:virology; D008168:Lung / Q000276:immunology* / Q000473:pathology / Q000821:virology; D008679:Metaplasia; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D017455:Receptors, IgE / Q000276:immunology*; D020545:Respiratory Mucosa / Q000473:pathology* / Q000821:virology; D019562:Viral Load; D014777:Virus Diseases / Q000276:immunology*
D017455:Receptors, IgE