MyD88 signaling is not essential for induction of antigen‐specific B cell responses but is indispensable for protection against Pneumonia infection following oral vaccination with attenuated Salmonella expressing PspA antigen

Abstract

Toll‐like receptors (TLRs) directly induce innate host defense responses, but the mechanisms of TLR‐mediated adaptive immunity remain subject to debate. In this study, we clarified the role of TLR‐mediated innate immunity for induction of adaptive immunity by oral vaccination with live recombinant attenuated Salmonella (S.) typhimurium vaccine (RASV) strain expressing Pneumonia surface protein A (PspA) antigen. Interestingly, oral vaccination with RASV expressing PspA resulted in identical levels of PspA‐specific IgG and IgA Ab responses in the serum and fecal extracts of MyD88−/− mice when compared with those of wild‐type C57BL/6 mice. In support of these results, similar numbers of PspA‐specific IgG and IgA Ab‐secreting cells were detected in the spleen and small and large intestines both of MyD88−/− mice and wild‐type mice. Moreover, Ag‐specific serum IgG and intestinal IgA Abs are normally induced in MyD88−/−TRIF−/− mice by oral immunization with attenuated Salmonella strain expressing PspA. Of most interest, MyD88 mediated signaling is crucial for efficient protection in both sepsis and lung pneumonia models. Taken together, these results suggest that innate immunity activated by MyD88 signals might not be necessary for antigen specific Ab induction but is critical for protection following oral vaccination with attenuated Salmonella expressing PspA.