Enteric reovirus infection stimulates peanut-specific IgG2a responses in a mouse food allergy model.
IgE-mediated food allergies are an important cause of life-threatening hypersensitivity reactions. Orally administered peanut antigens mixed with the mucosal adjuvant cholera toxin (CT) induce a strong peanut extract (PE)-specific serum IgE response that is correlated with T-helper type 1 (Th1) and type 2 (Th2)-like T-cell responses. This study was conducted to determine if respiratory enteric orphan virus (reovirus), a non-pathogenic virus that induces robust Th1-mediated mucosal and systemic responses could modulate induction of PE-specific allergic responses when co-administered with PE. Young mice were orally exposed to PE mixed with CT, reovirus, or both CT and reovirus. As expected, CT promoted PE-specific serum IgE, IgG1, and IgG2a and intestinal IgA production as well as splenic Th1- and Th2-associated cytokine recall responses. Reovirus did not alter PE-specific serum IgE and IgG1 levels, but substantially increased the PE-specific IgG2a response when co-administered with PE with or without CT. Additionally, reovirus significantly decreased the percentage of the Peyer's patch CD8+ T-cells and Foxp3+CD4+ T-regulatory cells when co-administered with PE. These results demonstrate that an acute mucosal reovirus infection and subsequent Th1 immune response is capable of modulating the Th1/Th2 controlled humoral response to PE. The reovirus-mediated increase in the PE-specific IgG2a antibody response may have therapeutic implications as increased levels of non-allergenic PE-specific IgG2a could block PE antigens from binding to IgE-sensitized mast cells.
Fecek
Ronald J
RJ
Department of Microbiology, Immunology, and Cell Biology, Robert C. Byrd Health Sciences Center of West Virginia University, Morgantown, P.O. Box 9177, WV 26506, USA.
Marcondes Rezende
Marisa
M
Busch
Ryan
R
Hassing
Ine
I
Pieters
Raymond
R
Cuff
Christopher F
CF
D000818:Animals; D010367:Arachis / Q000737:chemistry / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology; D002460:Cell Line; D002478:Cells, Cultured; D002772:Cholera Toxin / Q000276:immunology / Q000494:pharmacology; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000276:immunology / Q000821:virology; D007421:Intestine, Small / Q000187:drug effects / Q000276:immunology / Q000821:virology; D051379:Mice; D008809:Mice, Inbred C3H; D021183:Peanut Hypersensitivity / Q000276:immunology*; D010581:Peyer's Patches / Q000276:immunology / Q000821:virology; D010936:Plant Extracts / Q000276:immunology / Q000494:pharmacology; D012088:Reoviridae Infections / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology; D046509:Tissue Culture Techniques
D016207:Cytokines; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D010936:Plant Extracts; D002772:Cholera Toxin