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 AND CLINICAL RELEVANCE: 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.