Development of atopy by severe paramyxoviral infection in a mouse model. Ann Allergy Asthma Immunol 2010 Dec;105(6):437-443.e1
Date
12/07/2010Pubmed ID
21130381Pubmed Central ID
PMC3059126DOI
10.1016/j.anai.2010.09.010Scopus ID
2-s2.0-78649926556 (requires institutional sign-in at Scopus site) 27 CitationsAbstract
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.
CONCLUSION: 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.
Author List
Cheung DS, Ehlenbach SJ, Kitchens T, Riley DA, Grayson MHMESH terms used to index this publication - Major topics in bold
AllergensAnimals
Disease Models, Animal
Hypersensitivity, Immediate
Immunoglobulin E
Mice
Mice, Inbred C57BL
Mice, Knockout
Ovalbumin
Receptors, IgE
Respirovirus Infections
Sendai virus
