CXCL10/gamma interferon-inducible protein 10-mediated protection against Leishmania amazonensis infection in mice

Rene E. Vasquez, Lynn Soong

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)6769-6777
Number of pages9
JournalInfection and Immunity
Volume74
Issue number12
DOIs
StatePublished - Dec 2006

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Chemokine CXCL10
Leishmania
Interferon-gamma
Inbred C57BL Mouse
Chemokines
Parasites
Chemokine CCL2
Infection
CD4 Antigens
Cutaneous Leishmaniasis
Inbred Strains Mice
Proteins
Macrophage Activation
Interleukin-12
Infection Control
Interleukin-4
Interleukin-10
Nitric Oxide
Leukocytes
Lymph Nodes

ASJC Scopus subject areas

  • Immunology

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CXCL10/gamma interferon-inducible protein 10-mediated protection against Leishmania amazonensis infection in mice. / Vasquez, Rene E.; Soong, Lynn.

In: Infection and Immunity, Vol. 74, No. 12, 12.2006, p. 6769-6777.

Research output: Contribution to journalArticle

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