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 Chakour, R.
Right arrow Articles by Tacchini-Cottier, F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Chakour, R.
Right arrow Articles by Tacchini-Cottier, F.

 Previous Article  |  Next Article 

Infection and Immunity, September 2003, p. 5287-5295, Vol. 71, No. 9
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.9.5287-5295.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Both the Fas Ligand and Inducible Nitric Oxide Synthase Are Needed for Control of Parasite Replication within Lesions in Mice Infected with Leishmania major whereas the Contribution of Tumor Necrosis Factor Is Minimal

Reza Chakour,1,2 Reto Guler,3 Mélanie Bugnon,1,2 Cindy Allenbach,1,2 Irène Garcia,3 Jacques Mauël,2 Jacques Louis,1,2 and Fabienne Tacchini-Cottier1,2*

The World Health Organization Immunology Research and Training Center,1 Institute of Biochemistry, University of Lausanne, Epalinges,2 Department of Pathology, University of Geneva, Geneva, Switzerland3

Received 5 February 2003/ Returned for modification 8 April 2003/ Accepted 5 June 2003

Following infection with the protozoan parasite Leishmania major, C57BL/6 mice develop a small lesion that heals spontaneously. Resistance to infection is associated with the development of CD4+ Th1 cells producing gamma interferon (IFN-{gamma}) and tumor necrosis factor (TNF), which synergize in activating macrophages to their microbicidal state. We show here that C57BL/6 mice lacking both TNF and Fas ligand (FasL) (gld TNF-/- mice) infected with L. major neither resolved their lesions nor controlled Leishmania replication despite the development of a strong Th1 response. Comparable inducible nitric oxide synthase (iNOS) activities were detected in lesions of TNF-/-, gld TNF-/-, and gld mice, but only gld and gld TNF-/- mice failed to control parasite replication. Parasite numbers were high in gld mice and even more elevated in gld TNF-/- mice, suggesting that, in addition to iNOS, the Fas/FasL pathway is required for successful control of parasite replication and that TNF contributes only a small part to this process. Furthermore, FasL was shown to synergize with IFN-{gamma} for the induction of leishmanicidal activity within macrophages infected with L. major in vitro. Interestingly, TNF-/- mice maintained large lesion size throughout infection, despite being able to largely control parasite numbers. Thus, IFN-{gamma}, FasL, and iNOS appear to be essential for the complete control of parasite replication, while the contribution of TNF is more important in controlling inflammation at the site of parasite inoculation.

* Corresponding author. Mailing address: The WHO Immunology Research and Training Center, Institute of Biochemistry, University of Lausanne, 155 ch. des Boveresses, CH-1066 Epalinges, Switzerland. Phone: 41-21-692-57-07. Fax: 41-21-692-57-05. E-mail: Fabienne.Tacchini-Cottier{at}ib.unil.ch.

Editor: S. H. E. Kaufmann

Infection and Immunity, September 2003, p. 5287-5295, Vol. 71, No. 9
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.9.5287-5295.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Chakour, R., Allenbach, C., Desgranges, F., Charmoy, M., Mauel, J., Garcia, I., Launois, P., Louis, J., Tacchini-Cottier, F. (2009). A new function of the Fas-FasL pathway in macrophage activation. J. Leukoc. Biol. 86: 81-90 [Abstract] [Full Text]  
  • Mise-Omata, S., Kuroda, E., Sugiura, T., Yamashita, U., Obata, Y., Doi, T. S. (2009). The NF-{kappa}B RelA Subunit Confers Resistance to Leishmania major by Inducing Nitric Oxide Synthase 2 and Fas Expression but Not Th1 Differentiation. J. Immunol. 182: 4910-4916 [Abstract] [Full Text]  
  • McFarlane, E., Perez, C., Charmoy, M., Allenbach, C., Carter, K. C., Alexander, J., Tacchini-Cottier, F. (2008). Neutrophils Contribute to Development of a Protective Immune Response during Onset of Infection with Leishmania donovani. Infect. Immun. 76: 532-541 [Abstract] [Full Text]  
  • Rocha, F. J. S., Schleicher, U., Mattner, J., Alber, G., Bogdan, C. (2007). Cytokines, Signaling Pathways, and Effector Molecules Required for the Control of Leishmania (Viannia) braziliensis in Mice. Infect. Immun. 75: 3823-3832 [Abstract] [Full Text]  
  • Charmoy, M., Megnekou, R., Allenbach, C., Zweifel, C., Perez, C., Monnat, K., Breton, M., Ronet, C., Launois, P., Tacchini-Cottier, F. (2007). Leishmania major induces distinct neutrophil phenotypes in mice that are resistant or susceptible to infection. J. Leukoc. Biol. 82: 288-299 [Abstract] [Full Text]  
  • de Oliveira, G. M., Diniz, R. L., Batista, W., Batista, M. M., Bani Correa, C., de Araujo-Jorge, T. C., Henriques-Pons, A. (2007). Fas Ligand-Dependent Inflammatory Regulation in Acute Myocarditis Induced by Trypanosoma cruzi Infection. Am. J. Pathol. 171: 79-86 [Abstract] [Full Text]  
  • Carmona, E. M., Vassallo, R., Vuk-Pavlovic, Z., Standing, J. E., Kottom, T. J., Limper, A. H. (2006). Pneumocystis Cell Wall beta-Glucans Induce Dendritic Cell Costimulatory Molecule Expression and Inflammatory Activation through a Fas-Fas Ligand Mechanism. J. Immunol. 177: 459-467 [Abstract] [Full Text]  
  • Allenbach, C., Zufferey, C., Perez, C., Launois, P., Mueller, C., Tacchini-Cottier, F. (2006). Macrophages Induce Neutrophil Apoptosis through Membrane TNF, a Process Amplified by Leishmania major.. J. Immunol. 176: 6656-6664 [Abstract] [Full Text]  
  • Eidsmo, L., Nylen, S., Khamesipour, A., Hedblad, M.-A., Chiodi, F., Akuffo, H. (2005). The Contribution of the Fas/FasL Apoptotic Pathway in Ulcer Formation during Leishmania major-Induced Cutaneous Leishmaniasis. Am. J. Pathol. 166: 1099-1108 [Abstract] [Full Text]  
  • Guizani-Tabbane, L., Ben-Aissa, K., Belghith, M., Sassi, A., Dellagi, K. (2004). Leishmania major Amastigotes Induce p50/c-Rel NF-{kappa}B Transcription Factor in Human Macrophages: Involvement in Cytokine Synthesis. Infect. Immun. 72: 2582-2589 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»