Main

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).

Figure 1: Antibody responses.
figure 1

T-cell-dependent antibody responses in wild-type C57BL/6 mice (yellow) and in MyD88−/−/TRIFLps2/Lps2 double-knockout mice (red), which lack Toll-like-receptor activity. Young adult mice were given 100 μg endotoxin-free trinitrophenol–haemocyanin conjugates in alum. At day 7 post-immunization, serum antibody responses of the antibody isotypes IgM, IgG1, IgG2c, IgG2b and IgG3 were quantified by using an enzyme-linked immunosorbent assay, with titres representing the dilution giving half-maximal optical density. Means and standard errors are shown for six mice per group. Sera from unimmunized C57BL/6 mice (blue) establish the background of the assay.

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.