Immunity & infection
Infection of mice with pathogenic Salmonella activates innate immune receptors including Toll-like receptors (TLRs) and Nod-like receptors (NLRs) leading to secretion of inflammatory cytokines and chemokines. These inflammatory responses while contributing to innate immunity also bring about splenomegaly largely through expansion of immature reticulocytes. Whether these changes in splenic cellularity influence immune responses to non-Salmonella antigens that an infected host might encounter during this period has not been studied. Here, we show that infection of mice with live but not antibiotic - treated Salmonella Typhi produced an early inflammatory response that led to splenomegaly accompanied by increased numbers of TER119+ reticulocytes and F4/80+ macrophages, and reduced numbers of T and B lymphocytes. These changes, mediated through signaling from the TLR adaptor MyD88, did not affect antibody response to Salmonella, and both WT and MyD88 deficient mice produced comparable levels of antibodies. However, mice infected with Salmonella responded poorly to tetanus toxoid (TT) and ovalbumin administered at the time of splenomegaly. The ability of mice to elicit antibodies to non-Salmonella antigens was restored only after reversion of splenic cellularity back to normal state. These results suggest that changes in splenic cellularity brought about by infection with Salmonella might have previously unappreciated impact on immune response to non-Salmonella antigens. These findings have significant implications for host defence against other pathogens during typhoid fever and vaccine development against pathogenic Salmonella.