Freund adjuvant induces TLR2 but not TLR4 expression in the liver of mice (1)
The use of incomplete (IFA) and complete Freund adjuvant (CFA), which is heat-killed Mycobacterium tuberculosis bacilli (Mtb) dissolved in IFA, have been used extensively to establish experimental animal models of autoimmune diseases, e.g. experimental autoimmune encephalitis (EAE), neuritis (EAN), uveitis (EAU), thyroiditis (EAT) and orchitis, and to pro- duce antibodies. The liver is highly responsive to microbial toxins and part of this respon- siveness is mediated through its expression of toll-like receptors (TLRs).
C57BL/6J mice of both sexes were challenged with a single intraperitoneal injection of either CFA or IFA. Both CFA and IFA elicited an acute phase response in the liver as evidenced by a 5–10-fold increase in positive acute phase reactants such as acid a1-glycoprotein (AGP) and haptoglobin (Hp) and mRNA. There was no significant difference in the response between males and females. The baseline TLR2 mRNA level in the liver was undetectable. Four to six hours after administration of either CFA or IFA, TLR2 mRNA level in the liver increased 8 – 10 times above baseline. By 48 h, TLR2 mRNA level had returned to near basal level. Unlike TLR2, TLR4 expression in the liver was not induced by either the complete or incomplete adjuvant.
IFA itself is pharmacologically and immunologically active. IFA, which is composed of paraffin oil with mannide monooleate, a surfactant, has been known to stimulate innate immunity, induce expres- sion of cytokines, enhance phagocytosis, trigger autoimmune-like disease. The induction of TLR2 but not TLR4 may be an important reason for the success of Freund adjuvant since heat-killed Mtb activates TLR2 but not TLR4 while viable Mtb activates both TLR2 and TLR4 .