Acquired, but not innate, immune responses to Streptococcus pneumoniae arecompromised by neutralization of CD40L

Streptococcus pneumoniae is a significant pathogen of young children and th e elderly. Systemic infection by pneumococci is a complex process involving several bacterial and host factors. We have investigated the role of CD40L in host defense against pneumococcal infection. Treatment of mice with MR- I antibody (anti-CD154/CD40L) markedly reduced antibody responses to the pn eumococcal protein PspA, elicited by immunization of purified protein or wh ole bacteria. In mice immunized with whole bacteria, MR-1 treatment reduced antibody responses to capsular polysaccharides but not cell wall polysacch arides. MR-1 did not suppress antibody responses to isolated capsular polys accharides but did reduce the production of antibody to a capsular polysacc haride-protein conjugate, indicating that when presented in the context of whole bacteria, the humoral response to capsular polysaccharides is partial ly T-cell dependent. Despite the reduction of the protective humoral respon ses to pneumococcal infection, administration of MR-1 had no effect on seps is, lung infection, or nasal carriage in nonimmune mice inoculated with vir ulent pneumococci. Thus, short-term neutralization of CD40L does not compro mise innate host defenses against pneumococcal invasion.