Leishmania major abrogates gamma interferon-induced gene expression in human macrophages from a global perspective

Infection with Leishmania major triggers several pathways in the host cell that are crucial to initial infection as well as those that are used by Leishmania to enhance its replication and virulence. To identify the molecular events of the host cell in response to Leishmania, the global gene expression of the human monocytic cell line THP-1 either infected with Leishmania major in the presence and absence of gamma interferon (IFN-gamma) or in the presence of IFN-gamma alone was analyzed using high-density human oligonucleotide microarrays, followed by statistical analysis. The persistence of the parasite despite an extensive response to IFN-gamma, added 24 h after infection with L. major, suggests that L. major can survive in an IFN-gamma-enriched environment in vitro. Results demonstrate that L. major counteracts the IFN-gamma 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.