Disruption of CD40-CD40 ligand interactions results in an enhanced susceptibility to Leishmania amazonensis infection

Lynn Soong, Jian Chao Xu, Iqbal S. Grewal, Peter Kima, Jiaren Sun, B. Jack Longley, Nancy H. Ruddle, Diane McMahon-Pratt, Richard A. Flavell

Research output: Contribution to journalArticlepeer-review

258 Scopus citations

Abstract

To study the role of CD40 ligand (CD40L) in the host immune responses against intracellular pathogens, we infected CD40L knockout (CD40L(-/-)) mice with Leishmania amazonensis. Although wild-type mice were susceptible to infection and developed progressive ulcerative lesions, tissue parasite burdens in CD40L(-/-) mice were significantly higher. This heightened susceptibility to infection was associated with an impaired T cell and macrophage activation and altered inflammatory response, as reflected by low levels of IFNγ, lymphotoxin-tumor necrosis factor (LT-TNF), and nitric oxide (NO) production. Furthermore, CD40L(-/-) mice failed to generate a protective immune response after immunization. These results indicate an essential role of cognate CD40-CD40L interactions in the generation of cellular immune responses against an intracellular parasite.

Original languageEnglish (US)
Pages (from-to)263-273
Number of pages11
JournalImmunity
Volume4
Issue number3
DOIs
StatePublished - Mar 1996
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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