IAI FigSearch
Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Chaussabel, D.
Right arrow Articles by Vray, B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Chaussabel, D.
Right arrow Articles by Vray, B.

 Previous Article  |  Next Article 

Infection and Immunity, April 1999, p. 1929-1934, Vol. 67, No. 4
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

CD40 Ligation Prevents Trypanosoma cruzi Infection through Interleukin-12 Upregulation

Damien Chaussabel,1 Frédérique Jacobs,1 Jan de Jonge,2 Marijke de Veerman,2 Yves Carlier,3 Kris Thielemans,2 Michel Goldman,1 and Bernard Vray1,*

Laboratoire d'Immunologie Expérimentale1 and Laboratoire de Parasitologie,3 Faculté de Médecine, Université Libre de Bruxelles, and Laboratorium Fysiologie, Faculteit Geneeskunde, Vrije Universiteit Brussel,2 Brussels, Belgium

Received 14 September 1998/Returned for modification 19 October 1998/Accepted 21 January 1999

Because of the critical role of the CD40-CD40 ligand (CD40L) pathway in the induction and effector phases of immune responses, we investigated the effects of CD40 ligation on the control of Trypanosoma cruzi infection. First, we observed that supernatants of murine spleen cells stimulated by CD40L-transfected 3T3 fibroblasts (3T3-CD40L transfectants) prevent the infection of mouse peritoneal macrophages (MPM) by T. cruzi. This phenomenon depends on de novo production of nitric oxide (NO) as it is prevented by the addition of N-nitro-L-arginine methyl ester, a NO synthase inhibitor. NO production requires interleukin (IL)-12-mediated gamma interferon (IFN-gamma ) and tumor necrosis factor alpha (TNF-alpha ) synthesis as demonstrated by inhibition experiments using neutralizing anti-IL-12, anti-IFN-gamma , and anti-TNF-alpha monoclonal antibodies (MAb). We found that an activating anti-CD40 MAb also directly stimulates IFN-gamma -activated MPM to produce NO and thereby to control T. cruzi infection. To determine the in vivo relevance of these in vitro findings, mice were injected with 3T3-CD40L transfectants or 3T3 control fibroblasts at the time of T. cruzi inoculation. We observed that in vivo CD40 ligation dramatically reduced both parasitemia and the mortality rate of T. cruzi-infected mice. A reduced parasitemia was still observed when the injection of 3T3-CD40L transfectants was delayed 8 days postinfection. It was abolished by injection of anti-IL-12 MAb. Taken together, these data establish that CD40 ligation facilitates the control of T. cruzi infection through a cascade involving IL-12, IFN-gamma , and NO.

* Corresponding author. Mailing address: Laboratoire d'Immunologie Expérimentale (CP 615), Faculté de Médecine, Université Libre de Bruxelles, route de Lennik, B-1070 Brussels, Belgium. Phone: 32-2-555.62.60. Fax: 32-2-555.63.60. E-mail: bvray{at}med.ulb.ac.be.

Infection and Immunity, April 1999, p. 1929-1934, Vol. 67, No. 4
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:



Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
J. Bacteriol. J. Virol. Eukaryot. Cell
Microbiol. Mol. Biol. Rev. Clin. Vaccine Immunol. All ASM Journals

Copyright © 1999 by the American Society for Microbiology. All rights reserved.