title: Histoplasma capsulatum inhibits apoptosis and Mac-1 expression in leucocytes.
abstract: Histoplasma capsulatum is a fungus found intracellularly in neutrophils and peripheral blood mononuclear cells (PBMCs), suggesting that it is capable of evading damage and survives inside these cells. In this study, we report that neutrophils from H. capsulatum-infected mice, and human neutrophils and mononuclear cells exposed to H. capsulatum presented less apoptosis than those from noninfected animals or cells exposed to medium only. Moreover, cells harvested from infected animals are resistant to apoptosis induced by dexamethasone - a proapoptotic stimulant. We also show that neutrophils harvested from infected mice and PBMCs from humans exposed to the fungus had a greatly decreased Mac-1 expression. We conclude that H. capsulatum induces an antiapoptotic state on leucocytes, which correlates with decreased cell-surface Mac-1 expression. These facts may represent an escape mechanism for the fungus by delaying cell death and allowing the fungus to survive inside leucocytes.
authors.affiliation: Department of Clinical Analyses, Toxicology and Bromatology, School of Pharmaceutical Sciences of Ribeirão Preto, SP, Brazil.
authors.forename: A I
authors.initials: AI
authors.lastname: Medeiros
authors.forename: V L D
authors.initials: VL
authors.lastname: Bonato
authors.forename: A
authors.initials: A
authors.lastname: Malheiro
authors.forename: A R V
authors.initials: AR
authors.lastname: Dias
authors.forename: C L
authors.initials: CL
authors.lastname: Silva
authors.forename: L H
authors.initials: LH
authors.lastname: Faccioli
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002634:Chemotaxis, Leukocyte; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D015966:Gene Expression Regulation, Fungal; D006658:Histoplasma / Q000502:physiology*; D006660:Histoplasmosis / Q000276:immunology / Q000473:pathology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000382:microbiology*; D016177:Macrophage-1 Antigen / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D009504:Neutrophils / Q000378:metabolism / Q000382:microbiology*; D010538:Peritonitis / Q000276:immunology / Q000382:microbiology / Q000473:pathology
chemical_list: D016177:Macrophage-1 Antigen; D003907:Dexamethasone