title: Toll-like receptor 2 activators modulate oral tolerance in mice.
abstract: BACKGROUND
  Toll-like receptor 2 (TLR2) is a widely expressed pattern recognition receptor critical for innate immunity. TLR2 is also a key regulator of mucosal immunity implicated in the development of allergic disease. TLR2 activators are found in many common foods, but the role of TLR2 in oral tolerance and allergic sensitization to foods is not well understood.
  
  
  OBJECTIVE
  The purpose of this study was to evaluate the impacts of TLR2 expression and TLR2 activation on oral tolerance to food antigens in a murine model.
  
  
  METHODS
  Mice were fed ovalbumin (OVA) or peanut butter with or without the addition of low doses of TLR2 activators Pam3 CSK4 or FSL-1. Oral tolerance was assessed by analysing antibody responses after a systemic antigen challenge. OVA-specific Tregs were assessed in the Peyer's patches, mesenteric lymph nodes, and spleen in wild-type and TLR2(-/-) mice. Low-dose Pam3 CSK4 was also tested as an oral adjuvant.
  
  
  RESULTS
  Oral tolerance was successfully induced in both wild-type and TLR2(-/-) recipient mice, with an associated regulatory T-cell response. Oral TLR2 activation, with low-dose Pam3 CSK4 or FSL-1, during oral antigen exposure was found to alter oral tolerance and was associated with the development of substantial IgE and IgA responses to foods upon systemic challenge. Low-dose oral Pam3 CSK4 treatment also selectively enhanced antigen-specific IgA responses to oral antigen exposure.
  
  
  CONCLUSIONS
  TLR2 is not necessary for oral tolerance induction, but oral TLR2 activation modulates humoral IgE and IgA responses during tolerance development. Low-dose Pam3 CSK4 is also an effective oral adjuvant that selectively enhances IgA production. These observations are pertinent to the optimization of oral allergen immunotherapy and oral vaccine development.
authors.affiliation: Department of Microbiology and Immunology, Dalhousie University, Halifax, NS, Canada.|Dalhousie Inflammation Group, Dalhousie University, Halifax, NS, Canada.
authors.forename: M C
authors.initials: MC
authors.lastname: Tunis
authors.affiliation: Dalhousie Inflammation Group, Dalhousie University, Halifax, NS, Canada.|Department of Pathology, Dalhousie University, Halifax, NS, Canada.
authors.forename: B
authors.initials: B
authors.lastname: Dawod
authors.affiliation: Department of Microbiology and Immunology, Dalhousie University, Halifax, NS, Canada.|Dalhousie Inflammation Group, Dalhousie University, Halifax, NS, Canada.
authors.forename: K R
authors.initials: KR
authors.lastname: Carson
authors.affiliation: Department of Microbiology and Immunology, Dalhousie University, Halifax, NS, Canada.|Dalhousie Inflammation Group, Dalhousie University, Halifax, NS, Canada.
authors.forename: L L
authors.initials: LL
authors.lastname: Veinotte
authors.affiliation: Department of Microbiology and Immunology, Dalhousie University, Halifax, NS, Canada.|Dalhousie Inflammation Group, Dalhousie University, Halifax, NS, Canada.|Department of Pathology, Dalhousie University, Halifax, NS, Canada.
authors.forename: J S
authors.initials: JS
authors.lastname: Marshall
mesh_terms: D000276:Adjuvants, Immunologic; D000485:Allergens / Q000276:immunology*; D000818:Animals; D004075:Diglycerides / Q000494:pharmacology; D004195:Disease Models, Animal; D005502:Food / Q000009:adverse effects*; D005512:Food Hypersensitivity / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D007108:Immune Tolerance / Q000187:drug effects / Q000235:genetics; D056724:Immunity, Humoral / Q000187:drug effects; D007070:Immunoglobulin A / Q000276:immunology; D055666:Lipopeptides / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D009842:Oligopeptides / Q000494:pharmacology; D010047:Ovalbumin / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000819:agonists* / Q000235:genetics / Q000378:metabolism
chemical_list: D000276:Adjuvants, Immunologic; D000485:Allergens; D004075:Diglycerides; C460864:FSL-1 lipoprotein, synthetic; D007070:Immunoglobulin A; D055666:Lipopeptides; D009842:Oligopeptides; C508075:Pam(3)CSK(4) peptide; D051195:Toll-Like Receptor 2; D010047:Ovalbumin
keywords: Allergy; IgA; IgE; TLR2; Treg; murine; oral tolerance; ovalbumin; peanut