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.
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.
Authors: Anand C Patel; Jeffrey D Morton; Edy Y Kim; Yael Alevy; Suzanne Swanson; Jennifer Tucker; Guaming Huang; Eugene Agapov; Thomas E Phillips; Maria E Fuentes; Antonio Iglesias; Dee Aud; John D Allard; Karim Dabbagh; Gary Peltz; Michael J Holtzman Journal: Physiol Genomics Date: 2006-03-28 Impact factor: 3.107
Authors: Robin Stephens; David A Randolph; Guangming Huang; Michael J Holtzman; David D Chaplin Journal: J Immunol Date: 2002-11-15 Impact factor: 5.422
Authors: R Stokes Peebles; Koichi Hashimoto; Jason D Morrow; Ryszard Dworski; Robert D Collins; Yuko Hashimoto; John W Christman; Kyung-Ho Kang; Kasia Jarzecka; Jamye Furlong; Daphne B Mitchell; Megha Talati; Barney S Graham; James R Sheller Journal: Am J Respir Crit Care Med Date: 2002-04-15 Impact factor: 21.405
Authors: E Hamelmann; G Cieslewicz; J Schwarze; T Ishizuka; A Joetham; C Heusser; E W Gelfand Journal: Am J Respir Crit Care Med Date: 1999-09 Impact factor: 21.405
Authors: R S Peebles; K Hashimoto; R D Collins; K Jarzecka; J Furlong; D B Mitchell; J R Sheller; B S Graham Journal: J Infect Dis Date: 2001-11-13 Impact factor: 5.226
Authors: Xiuxu Chen; Daniel Leach; Desiré A Hunter; Daniel Sanfelippo; Erika J Buell; Sarah J Zemple; Mitchell H Grayson Journal: Open Immunol J Date: 2011
Authors: Monica A Thomas; Becky J Buelow; Amanda M Nevins; Stephanie E Jones; Francis C Peterson; Rebekah L Gundry; Mitchell H Grayson; Brian F Volkman Journal: J Biol Chem Date: 2015-01-02 Impact factor: 5.157