Host response and Histoplasma capsulatum/macrophage molecular interactions.
Histoplasma capsulatum is the etiological agent of histoplasmosis, a chronic respiratory infection that is generally asymptomatic in healthy individuals, but severe or fatal in patients who are immunosuppressed or otherwise debilitated. H. capsulatum is found as a mould in soil and becomes a pathogenic yeast in the mammalian host. The first line of defense that H. capsulatum faces during host invasion is the attack of polymorphonuclear neutrophils and resident macrophages. In animal models, once phagocytosed, H. capsulatum is not killed by fusion of the phago-lysosomes, instead it multiplies within non-activated macrophages and destroys them. Upon induction of cell-mediated immunity, cytokines activate macrophages and destroy the yeast cells. Some aspects of the fungus-macrophage interaction have been elucidated, and it is clear that some of the mechanisms by which H. capsulatum escapes the lethal effects of this very hostile environment, involve the regulation of specific genes. Recently, using the differential display reverse transcriptase polymerase chain reaction technique, a number of H. capsulatum genes that are induced after the yeasts are ingested by macrophages have been identified. However, the mechanisms that underlie the capacity of H. capsulatum to adapt to the new environmental conditions present in macrophages remain to be clarified.
Porta
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International Institute of Genetics and Biophysics, Naples, Italy.
Maresca
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D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D005800:Genes, Fungal / Q000235:genetics; D006658:Histoplasma / Q000235:genetics / Q000472:pathogenicity*; D006660:Histoplasmosis / Q000276:immunology* / Q000382:microbiology; D006801:Humans; D007111:Immunity, Cellular; D007113:Immunity, Innate; D008172:Lung Diseases, Fungal / Q000276:immunology* / Q000382:microbiology; D008264:Macrophages / Q000276:immunology / Q000382:microbiology*; D010587:Phagocytosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha