Generation of nitric oxide by the inducible nitric oxide synthase protects gamma delta T cells from Mycobacterium tuberculosis-induced apoptosis

C. Sciorati, P. Rovere, M. Ferrarini, C. Paolucci, S. Heltai, R. Vaiani, E. Clementi, A. A. Manfredi

Research output: Contribution to journalArticlepeer-review

Abstract

Gamma delta T cells are early recruited into mycobacterial lesions. Upon microbial antigen recognition, gamma delta cells secrete cytokines and chemokines and undergo apoptosis via CD95/CD95 ligand (CD95L) interaction, possibly influencing the outcome of infection and the characteristics of the disease. In this paper we show that activated phagocytes acquire, upon challenge with Mycobacterium tuberculosis, the ability to inhibit M. tuberculosis-induced gamma delta cell apoptosis. Apoptosis protection was due to NO because it correlated with NO synthase (NOS)-2 induction and activity in scavenger cells and was abrogated by NOS inhibitors. Furthermore, the NO donor S-nitrosoacetylpenicillamine mimicked the effect of enzyme induction. NO left unaffected the expression of CD95 and CD95L, suggesting interference with an event ensuing CD95/CD95L interaction. NO was found to interfere with the intracellular accumulation of ceramide and the activation of caspases, which were involved in gamma delta T cells apoptosis after M. tuberculosis recognition. We propose that NO generated by infected macrophages determines the life span and, therefore, the function of lymphocytes at the infection site, thus linking innate and adaptive immunity.

Original languageEnglish
Pages (from-to)509
Number of pages1
JournalInternational Journal of Leprosy and Other Mycobacterial Diseases
Volume67
Issue number4 SUPPL.
Publication statusPublished - 1999

ASJC Scopus subject areas

  • Dermatology

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