Development of atopy by severe paramyxoviral infection in a mouse model.
BACKGROUND
Atopic diseases have been increasing in prevalence, yet the initial inciting events that lead to atopy are not understood. Paramyxoviral infections have been suggested to play a role; however, much of these data are correlative.


OBJECTIVE
To determine whether exposure to a nonviral antigen during a paramyxoviral infection is sufficient to drive IgE production against the bystander antigen and whether clinical disease against this antigen would result.


METHODS
Wild-type C57BL6 mice or mice deficient in FcεRIα (FcεRIα(-/-)) or IgE (IgE(-/-)) were inoculated with Sendai virus (SeV) or UV-inactivated SeV (UV-SeV) and subsequently exposed to ovalbumin (OVA) intranasally. Mice were further challenged 3 times with intranasal OVA on days 20 to 22 after inoculation with SeV, and airway hyperreactivity and mucous cell metaplasia were determined.


RESULTS
Exposure to OVA during SeV infection led to significant OVA specific IgE production (median, 548 vs 0 ng/mL; P = .03; SeV vs UV-SeV). This induction of OVA specific IgE production depended on FcεRI because FcεRIα(-/-) mice produced significantly less IgE (112 ng/mL; P = .03; vs wild-type mice). Furthermore, in wild-type mice OVA exposure and challenge significantly enhanced SeV-induced airway hyperreactivity and mucous cell metaplasia, but this failed to occur in either FcεRIα(-/-) or IgE(-/-) mice.


CONCLUSIONS
A single exposure to a bystander allergen during a paramyxoviral infection is sufficient to drive allergen specific IgE production in a partial FcεRI-dependent mechanism. These data begin to provide mechanistic insight into how viral infections might drive development of atopic disease.
Medical College of Wisconsin, MACC Fund Research Center, Milwaukee, WI 53226, USA.
Dorothy S
DS
Cheung
Sarah J
SJ
Ehlenbach
Tom
T
Kitchens
Desire A
DA
Riley
Mitchell H
MH
Grayson
D000485:Allergens / Q000276:immunology*; D000818:Animals; D004195:Disease Models, Animal; D006969:Hypersensitivity, Immediate / Q000097:blood / Q000276:immunology*; D007073:Immunoglobulin E / Q000097:blood / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology; D017455:Receptors, IgE / Q000235:genetics; D010253:Respirovirus Infections / Q000276:immunology*; D029082:Sendai virus / Q000276:immunology*
D000485:Allergens; D017455:Receptors, IgE; D007073:Immunoglobulin E; D010047:Ovalbumin