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Infection and Immunity, December 2006, p. 6769-6777, Vol. 74, No. 12
0019-9567/06/$08.00+0     doi:10.1128/IAI.01073-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

CXCL10/Gamma Interferon-Inducible Protein 10-Mediated Protection against Leishmania amazonensis Infection in Mice{triangledown}

Rene E. Vasquez1 and Lynn Soong1,2*

Departments of Microbiology and Immunology,1 Pathology, Center for Biodefense and Emerging Infectious Diseases, Sealy Center for Vaccine Development, Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, Texas 77555-10702

Received 9 July 2006/ Returned for modification 9 August 2006/ Accepted 12 September 2006

Leishmania amazonensis can cause progressive disease in most inbred strains of mice. We have previously shown that L. amazonensis-infected C57BL/6 mice have profound impairments in expression of proinflammatory cytokines and chemokines and in activation of antigen-specific CD4+ T cells. These impairments are independent of interleukin-4 (IL-4) but partially due to IL-10 production. The precise mechanism of pathogenesis associated with L. amazonensis infection remains largely unresolved. Since chemokines are essential mediators of leukocyte recruitment and effector cell function, we hypothesized that these molecules are important for the initiation of early responses locally and for the eventual control of the infection. In this study, we examined the roles of CXCL10/gamma interferon-inducible protein 10 (IP-10) and CCL2/monocyte chemoattractant protein 1 (MCP-1) in the activation of the macrophage effector function in vitro and their efficacy in ameliorating infection in vivo. Bone marrow-derived macrophages of both BALB/c and C57BL/6 mice were treated with increasing concentrations of recombinant chemokines prior to infection with either stationary-phase promastigotes or tissue-derived amastigotes. We found that treatment with IP-10 or MCP-1 significantly reduced parasite burdens, in a dose-dependent manner, and triggered nitric oxide production. When susceptible C57BL/6 mice were injected locally with IP-10 following L. amazonensis infection, there was a significant delay in lesion development and a reduction in parasite burdens, accompanied by 7- and 3.5-fold increases in gamma interferon and IL-12 secretion, respectively, in restimulated lymph node cells. This study confirms that IP-10 plays a protective role in promoting the reduction of intracellular parasites and thereby opens new avenues for therapeutic control of nonhealing cutaneous leishmaniasis in the New World.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, University of Texas Medical Branch, Medical Research Building 3.132, 301 University Blvd., Galveston, TX 77555-1070. Phone: (409) 772-8149. Fax: (409) 747-6869. E-mail: lysoong{at}utmb.edu.

{triangledown} Published ahead of print on 18 September 2006.

Editor: W. A. Petri, Jr.

Infection and Immunity, December 2006, p. 6769-6777, Vol. 74, No. 12
0019-9567/06/$08.00+0     doi:10.1128/IAI.01073-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Sanabria, M. X. H., Vargas-Inchaustegui, D. A., Xin, L., Soong, L. (2008). Role of Natural Killer Cells in Modulating Dendritic Cell Responses to Leishmania amazonensis Infection. Infect. Immun. 76: 5100-5109 [Abstract] [Full Text]  
  • Vasquez, R. E., Xin, L., Soong, L. (2008). Effects of CXCL10 on Dendritic Cell and CD4+ T-Cell Functions during Leishmania amazonensis Infection. Infect. Immun. 76: 161-169 [Abstract] [Full Text]  
  • Wanasen, N., MacLeod, C. L., Ellies, L. G., Soong, L. (2007). L-Arginine and Cationic Amino Acid Transporter 2B Regulate Growth and Survival of Leishmania amazonensis Amastigotes in Macrophages. Infect. Immun. 75: 2802-2810 [Abstract] [Full Text]  


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