Leishmania majorAbrogates Gamma Interferon-Induced Gene Expression in Human Macrophages from a Global Perspective

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Abstract
Infection withLeishmania majortriggers several pathways in the host cell that are crucial to initial infection as well as those that are used byLeishmaniato enhance its replication and virulence. To identify the molecular events of the host cell in response toLeishmania, the global gene expression of the human monocytic cell line THP-1 either infected withLeishmania majorin the presence and absence of gamma interferon (IFN-γ) or in the presence of IFN-γ alone was analyzed using high-density human oligonucleotide microarrays, followed by statistical analysis. The persistence of the parasite despite an extensive response to IFN-γ, added 24 h after infection withL. major, suggests thatL. majorcan survive in an IFN-γ-enriched environment in vitro. Results demonstrate thatL. majorcounteracts the IFN-γ response in macrophages on a large scale. Expression of genes involved in the innate immune response, cell adhesion, proteasomal degradation, Toll-like receptor expression, a variety of signaling molecules, and matrix metalloproteinases was significantly modulated.