Acquired, but not innate, immune responses to Streptococcus pneumoniae are compromised by neutralization of CD40L.
Streptococcus pneumoniae is a significant pathogen of young children and the 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-1 antibody (anti-CD154/CD40L) markedly reduced antibody responses to the pneumococcal protein PspA, elicited by immunization of purified protein or whole bacteria. In mice immunized with whole bacteria, MR-1 treatment reduced antibody responses to capsular polysaccharides but not cell wall polysaccharides. MR-1 did not suppress antibody responses to isolated capsular polysaccharides but did reduce the production of antibody to a capsular polysaccharide-protein conjugate, indicating that when presented in the context of whole bacteria, the humoral response to capsular polysaccharides is partially T-cell dependent. Despite the reduction of the protective humoral responses to pneumococcal infection, administration of MR-1 had no effect on sepsis, lung infection, or nasal carriage in nonimmune mice inoculated with virulent pneumococci. Thus, short-term neutralization of CD40L does not compromise innate host defenses against pneumococcal invasion.
Hwang
Y i
Yi
Departments of Pediatrics, University of Rochester School of Medicine, Rochester, New York 14642, USA.
Nahm
M H
MH
Briles
D E
DE
Thomas
D
D
Purkerson
J M
JM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D023201:CD40 Ligand; D005260:Female; D007114:Immunization; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D011135:Polysaccharides, Bacterial / Q000276:immunology; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology; D013296:Streptococcus pneumoniae / Q000276:immunology*
D000911:Antibodies, Monoclonal; D008562:Membrane Glycoproteins; D011135:Polysaccharides, Bacterial; D018124:Receptors, Tumor Necrosis Factor; D023201:CD40 Ligand