General suppression of macrophage gene expression during Leishmania donovani infection.
Within the mammalian host, Leishmania donovani is an obligatory intracellular protozoan that resides and multiplies exclusively in the phagolysosomes of macrophages. The outcome of this infection is governed by the interaction between Leishmania and macrophage molecules that ultimately effect the expression of genes within both cells. To explore the effect of this intracellular infection on macrophage gene expression, a cDNA expression array analysis was performed to compare gene expression profiles in noninfected and L. donovani-infected macrophages. In this manner, it was possible to examine the effect of infection on the expression of several hundred well-characterized host cell genes in an unbiased manner. Interestingly, approximately 40% of the genes whose expression was detected in macrophages were down-regulated during infection with L. donovani. However, several genes were also induced during the infection process, some of which could play a role in recruitment of additional macrophages to the site of infection. Taken together, the general suppression of gene expression in addition to the selective induction of key genes is likely to play an important role in allowing the parasite to survive and proliferate within its host macrophage cell.
Buates
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S
Institute of Parasitology, McGill University, St. Anne de Bellevue, Quebec, Canada.
Matlashewski
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G
D000818:Animals; D015152:Blotting, Northern; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D019013:CD40 Antigens / Q000096:biosynthesis / Q000235:genetics; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D054407:Chemokine CCL4; D015536:Down-Regulation / Q000235:genetics* / Q000276:immunology*; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology*; D007893:Leishmania donovani / Q000254:growth & development / Q000276:immunology*; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis / Q000235:genetics; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism* / Q000469:parasitology; D051379:Mice; D008807:Mice, Inbred BALB C; D020411:Oligonucleotide Array Sequence Analysis; D016053:RNA, Protozoan / Q000032:analysis; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D014158:Transcription, Genetic / Q000276:immunology; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology
D019013:CD40 Antigens; C515335:Ccr2 protein, mouse; D018932:Chemokine CCL2; D054407:Chemokine CCL4; D019402:Macrophage Inflammatory Proteins; D016053:RNA, Protozoan; D054390:Receptors, CCR2; D019707:Receptors, Chemokine