Toll-free immune responses

Toll receptors mediate invertebrate protection against bacteria and yeast. Homologous mammalian molecules, the “Toll-like receptors” (TLR), were identified almost a decade ago and were immediately implicated in immunity and autoimmunity. TLRs were thought to provide crucial adjuvant stimulation to trigger the specific adaptive immune response. So you can imagine their surprise when Nemazee and colleagues found that mice mice without functional TLRs nevertheless made strong antibody responses against antigens in four typical adjuvants, including Freund’s Complete Adjuvant (FCA) (Figure). These mice were genetically deficient in both MyD88 and TRIF, which mediate all known TLR signaling. Mice were immunized with the antigen trinitrophenol - hemocyanin (TNP-Hy) in Freund's complete adjuvant. Similar results were obtained with another common experimental antigen, TNP-KLH (keyhole limpet hemocyanin). The deficient mice also responded normally following TNP-Hy immunization with the adjuvant alum, which is used in humans. Moreover, the TLR deficient mice also respond strongly against adjuvants containing TLR ligands. The authors modestly state that these findings “may have important implications in the use and development of vaccine adjuvants”.