CD40 ligation prevents Trypanosoma cruzi infection through interleukin- 12 upregulation

Damien J. Chaussabel, Frédérique Jacobs, Jan De Jonge, Marijke De Veerman, Yves Carlier, Kris Thielemans, Michel Goldman, Bernard Vray

Research output: Contribution to journalArticle

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Abstract

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-γ) and tumor necrosis factor alpha (TNF-α) synthesis as demonstrated by inhibition experiments using neutralizing anti-IL-12, anti-IFN-γ, and anti- TNF-α monoclonal antibodies (MAb). We found that an activating anti-CD40 MAb also directly stimulates IFN-γ-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-γ, and NO.

Original languageEnglish
Pages (from-to)1929-1934
Number of pages6
JournalInfection and Immunity
Volume67
Issue number4
Publication statusPublished - 1999
Externally publishedYes

Fingerprint

Trypanosoma cruzi
Interleukin-12
CD40 Ligand
Ligation
Up-Regulation
Nitric Oxide
Infection
Parasitemia
Monoclonal Antibodies
Peritoneal Macrophages
Fibroblasts
Injections
Nitric Oxide Synthase
Interferon-gamma
Spleen
Tumor Necrosis Factor-alpha
Mortality

ASJC Scopus subject areas

  • Immunology

Cite this

Chaussabel, D. J., Jacobs, F., De Jonge, J., De Veerman, M., Carlier, Y., Thielemans, K., ... Vray, B. (1999). CD40 ligation prevents Trypanosoma cruzi infection through interleukin- 12 upregulation. Infection and Immunity, 67(4), 1929-1934.

CD40 ligation prevents Trypanosoma cruzi infection through interleukin- 12 upregulation. / Chaussabel, Damien J.; Jacobs, Frédérique; De Jonge, Jan; De Veerman, Marijke; Carlier, Yves; Thielemans, Kris; Goldman, Michel; Vray, Bernard.

In: Infection and Immunity, Vol. 67, No. 4, 1999, p. 1929-1934.

Research output: Contribution to journalArticle

Chaussabel, DJ, Jacobs, F, De Jonge, J, De Veerman, M, Carlier, Y, Thielemans, K, Goldman, M & Vray, B 1999, 'CD40 ligation prevents Trypanosoma cruzi infection through interleukin- 12 upregulation', Infection and Immunity, vol. 67, no. 4, pp. 1929-1934.
Chaussabel DJ, Jacobs F, De Jonge J, De Veerman M, Carlier Y, Thielemans K et al. CD40 ligation prevents Trypanosoma cruzi infection through interleukin- 12 upregulation. Infection and Immunity. 1999;67(4):1929-1934.
Chaussabel, Damien J. ; Jacobs, Frédérique ; De Jonge, Jan ; De Veerman, Marijke ; Carlier, Yves ; Thielemans, Kris ; Goldman, Michel ; Vray, Bernard. / CD40 ligation prevents Trypanosoma cruzi infection through interleukin- 12 upregulation. In: Infection and Immunity. 1999 ; Vol. 67, No. 4. pp. 1929-1934.
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