Freund adjuvant induces TLR2 but not TLR4 expression in the liver of mice.
Freund adjuvants are used extensively to establish experimental animal models of autoimmune diseases and to produce antibodies. However, studies on their mechanisms of action have been largely neglected, particularly their effects on liver, the primary target organ for host-microbe interaction. Here we show that treatment with either complete (CFA) or incomplete (IFA) Freund adjuvant induced a 5-10-fold increase in toll-like receptor (TLR) 2 mRNA but not TLR4 mRNA in livers of mice. Since CFA is essentially made of killed Mycobacterium tuberculosis bacilli (Mtb) dissolved in IFA, it is the solvent in CFA that induced an increase in TLR2 expression. As TLR2 is the receptor activated by killed Mtb, this solvent-mediated increase in TLR2 expression will result in enhanced recognition of killed Mtb by hepatocytes during CFA administration. We propose that the potency of Freund adjuvant in eliciting an immune response lies in their ability to induce expression of the appropriate TLR, TLR2, for the active ingredient, killed Mtb, in CFA.
Lim
Sai-Kiang
SK
National University Medical Institutes and Genome Institute of Singapore, The National University of Singapore, Block MD11, 10 Medical Drive, Singapore 117597, Singapore. gislimsk@nus.edu.sg
D000818:Animals; D005260:Female; D005620:Freund's Adjuvant / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D051379:Mice; D009169:Mycobacterium tuberculosis; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D011956:Receptors, Cell Surface / Q000235:genetics*; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D005620:Freund's Adjuvant