Abstract
Arising from: C. Pasare & R. Medzhitov Nature 438, 364–368 (2005); Pasare & Medzhitov reply.
Microbial components, such as lipopolysaccharides, augment immune responses by activating Toll-like receptors (TLRs). Some have interpreted this to mean that TLR signalling might not only help to initiate the adaptive immune response, but may also be required for it1. The expanded view is shared by Pasare and Medzhitov2, who conclude from an analysis of mice deficient in MyD88 (a TLR-signalling adaptor protein) that the generation of T-dependent antigen-specific antibody responses requires activation of TLRs in B cells. However, we show here that robust antibody responses can be elicited even in the absence of TLR signals. This appreciable TLR-independence of immune responses should be taken into account in the rational design of immunogenic and toleragenic vaccines.
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In mice that lack both MyD88 and TRIF (another TLR-signalling adaptor protein), all known types of TLR signalling are absent3. We find that preimmune serum immunoglobulin concentrations are substantial in these mice, and that T-cell-dependent antibody responses to an antigen administered in alum are unimpaired (Fig. 1). It is notable that immunization with an antigen in alum, one of the few adjuvants approved for human use, promotes a TLR-independent antibody response. Further, we find that MyD88/TRIF double-deficient mice generate a robust antibody response to the T-independent antigen trinitrophenol–Ficoll (results not shown).
In the final analysis, we believe that Pasare and Medzhitov have simply demonstrated that TLR-dependent B-cell responses depend upon TLR signalling. But TLR signalling is clearly not essential for a response to typical vaccination.
References
Medzhitov, R. & Janeway, C. A. Jr Science 296, 298–300 (2002).
Pasare, C. & Medzhitov, R. Nature 438, 364–368 (2005).
Hoebe, K. et al. Nature 424, 743–748 (2003).
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Nemazee, D., Gavin, A., Hoebe, K. et al. Toll-like receptors and antibody responses. Nature 441, E4 (2006). https://doi.org/10.1038/nature04875
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DOI: https://doi.org/10.1038/nature04875
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