Enhanced Replication of Leishmania amazonensis Amastigotes in Gamma Interferon-Stimulated Murine Macrophages: Implications for the Pathogenesis of Cutaneous Leishmaniasis

Hai Qi, Jiaxiang Ji, Nanchaya Wanasen, Lynn Soong

Research output: Contribution to journalArticle

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Abstract

During Leishmania major infection in mice, gamma interferon (IFN-γ) plays an essential role in controlling parasite growth and disease progression. In studies designed to ascertain the role of IFN-γ in Leishmania amazonensis infection, we were surprised to find that IFN-γ could promote L. amazonensis amastigote replication in macrophages (MΦs), although it activated MΦs to kill promastigotes. The replication-promoting effect of IFN-γ on amastigotes was independent of the source and genetic background of MΦs, was apparently not affected by surface opsonization of amastigotes, was not mediated by interleukin-10 or transforming growth factor β, and was observed at different temperatures. Consistent with the different fates of promastigotes and amastigotes in IFN-γ-stimulated MΦs, L. amazonensis-specific Th1 transfer helped recipient mice control L. amazonensis infection established by promastigotes but not L. amazonensis infection established by amastigotes. On the other hand, IFN-γ could stimulate MΦs to limit amastigote replication when it was coupled with lipopolysaccharides but not when it was coupled with tumor necrosis factor alpha. Thus, IFN-γ may play a bidirectional role at the level of parasite-MΦ interactions; when it is optimally coupled with other factors, it has a protective effect against infection, and in the absence of such synergy it promotes amastigote growth. These results reveal a quite unexpected aspect of the L. amazonensis parasite and have important implications for understanding the pathogenesis of the disease and for developing vaccines and immunotherapies.

Original languageEnglish (US)
Pages (from-to)988-995
Number of pages8
JournalInfection and Immunity
Volume72
Issue number2
DOIs
StatePublished - Feb 2004

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Cutaneous Leishmaniasis
Leishmania
Interferons
Interferon-gamma
Macrophages
Infection
Parasites
Leishmania major
Transforming Growth Factors
Growth
Interleukin-10
Immunotherapy
Lipopolysaccharides
Disease Progression
Vaccines
Tumor Necrosis Factor-alpha
Temperature

ASJC Scopus subject areas

  • Immunology

Cite this

Enhanced Replication of Leishmania amazonensis Amastigotes in Gamma Interferon-Stimulated Murine Macrophages : Implications for the Pathogenesis of Cutaneous Leishmaniasis. / Qi, Hai; Ji, Jiaxiang; Wanasen, Nanchaya; Soong, Lynn.

In: Infection and Immunity, Vol. 72, No. 2, 02.2004, p. 988-995.

Research output: Contribution to journalArticle

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