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Infection and Immunity, October 1999, p. 5253-5257, Vol. 67, No. 10
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

CD40-CD40 Ligand Interactions Augment Survival of Normal Mice, but Not CD40 Ligand Knockout Mice, Challenged Orally with Salmonella dublin

Ian Marriott,1 Elaine K. Thomas,2 and Kenneth L. Bost1,*

Department of Biology, University of North Carolina at Charlotte, Charlotte, North Carolina 28223,1 and Immunex Corporation, Seattle, Washington 981012

Received 14 April 1999/Returned for modification 25 May 1999/Accepted 15 July 1999

Interactions between CD40 expressed on macrophages and CD40 ligand expressed on T lymphocytes can be an important signal for optimal macrophage activation. Previous studies have demonstrated that the optimal response against certain intracellular pathogens (e.g., Crytosporidium and Leishmania spp.) by macrophages requires CD40-CD40 ligand interactions. However, this finding is not universal, since two recent reports utilizing CD40 knockout mice have shown no such contribution to the protective immune response against Mycobacterium tuberculosis or Histoplasma capsulatum. We demonstrate here that CD40-CD40 ligand interactions are significant events in the protective response against the intracellular pathogen Salmonella dublin in normal mice but not for animals genetically deficient in CD40 ligand expression. Treating BALB/c mice exogenously with a CD40 agonist (i.e., soluble trimeric CD40 ligand) increased resistance against a lethal, orally administered dose of S. dublin. Conversely, in vivo administration of a monoclonal antibody against CD40 ligand to block endogenous CD40-CD40 ligand interactions resulted in a decreased resistance to salmonellosis. In contrast, CD40 ligand knockout mice demonstrated no increased susceptibility to salmonellosis. In vitro treatment of Salmonella-infected macrophages from BALB/c mice with soluble trimeric CD40 ligand resulted in an elevated production of interleukin 12p70 by these cells, suggesting a mechanism whereby CD40-CD40 ligand interactions might enhance protective immune responses to this pathogen. Taken together, these studies strongly suggest that CD40-CD40 ligand interactions in normal mice play an important protective role in immune responses against the gram-negative, intracellular pathogen S. dublin.


* Corresponding author. Mailing address: Department of Biology, University of North Carolina at Charlotte, 9201 University City Blvd., Charlotte, NC 28223. Phone: (704) 547-2909. Fax: (704) 547-3128. E-mail: klbost{at}emailuncc.edu.


Infection and Immunity, October 1999, p. 5253-5257, Vol. 67, No. 10
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.



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