title: The influence of low oxygen on macrophage response to Leishmania infection.
abstract: Hypoxia (low oxygen tension) is a common feature of inflamed and infected tissues. The influence of hypoxia on macrophage responses to micro-organisms has only recently been studied. This study demonstrates that hypoxia induced macrophages to control Leishmania amazonensis, an intracellular parasite that causes cutaneous and cutaneous metastatic lesions. The mechanisms that contribute to the control of macrophages against L. amazonensis infection under a hypoxic microenvironment are not known. Nitric oxide, TNF-α, IL-10 or IL-12 is not responsible for the decrease in parasitism under hypoxia. Live L. amazonensis entry or exocytosis of internalized particles as well as energetic metabolism was not impaired in infected macrophages; no apoptosis-like death was detected in intracellular parasites. Reactive oxygen species (ROS) is likely to be involved, because treatment with antioxidants N-acetylcysteine (NAC) and ebselen inhibits the leishmanicidal effect of macrophages under hypoxia. Leishmania amazonensis infection induces macrophages to express hypoxia-inducible factor-1 (HIF-1α) and -2 (HIF-2α). Data indicate that hypoxia affects the microbial activities and protein expression of macrophages leading to a different phenotype from that of the normoxic counterpart and that it plays a role in modulating Leishmania infection.
authors.affiliation: Department of Animal Biology, Universidade Estadual de Campinas, Campinas, São Paulo, Brazil.
authors.forename: A
authors.initials: A
authors.lastname: Degrossoli
authors.forename: W W
authors.initials: WW
authors.lastname: Arrais-Silva
authors.forename: M C
authors.initials: MC
authors.lastname: Colhone
authors.forename: F R
authors.initials: FR
authors.lastname: Gadelha
authors.forename: P P
authors.initials: PP
authors.lastname: Joazeiro
authors.forename: S
authors.initials: S
authors.lastname: Giorgio
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D001393:Azoles / Q000494:pharmacology; D051792:Basic Helix-Loop-Helix Proteins / Q000096:biosynthesis / Q000276:immunology; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology; D000860:Hypoxia / Q000276:immunology* / Q000378:metabolism; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology; D018664:Interleukin-12 / Q000276:immunology; D054833:Isoindoles; D016773:Leishmaniasis, Cutaneous / Q000276:immunology* / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000648:ultrastructure; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000276:immunology; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000276:immunology; D016566:Organoselenium Compounds / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D000111:Acetylcysteine; D001393:Azoles; D051792:Basic Helix-Loop-Helix Proteins; D016166:Free Radical Scavengers; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D016753:Interleukin-10; D018664:Interleukin-12; D054833:Isoindoles; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D016566:Organoselenium Compounds; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D000099162:Endothelial PAS Domain-Containing Protein 1; C497443:Hif1a protein, mouse; C042986:ebselen