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Infection and Immunity, February 2000, p. 511-517, Vol. 68, No. 2
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Acquired, but Not Innate, Immune Responses to Streptococcus pneumoniae Are Compromised by Neutralization of CD40L

Young-il Hwang,1,dagger Moon H. Nahm,1,2,3,4 David E. Briles,5 David Thomas,6,Dagger and Jeffrey M. Purkerson1,*

Departments of Pediatrics,1 Pathology,2 Medicine,3 and Microbiology and Immunology,4 University of Rochester School of Medicine, Rochester, New York; Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama5; and Biogen Corp., Cambridge, Massachusetts6

Received 26 July 1999/Returned for modification 14 October 1999/Accepted 3 November 1999

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.

* Corresponding author. Mailing address: Department of Pediatrics, University of Rochester School of Medicine, 601 Elmwood Ave., Box 777, Rochester, NY 14642. Phone: (716) 273-4697. Fax: (716) 271-7512. E-mail: Jeffrey_Purkerson{at}urmc.rochester.edu.

dagger Present address: Department of Anatomy, College of Medicine, Seoul National University, Seoul 110-799, Korea.

Dagger Present address: Tanox, Inc., Houston, TX 77025.

Infection and Immunity, February 2000, p. 511-517, Vol. 68, No. 2
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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