1. The Influence of Low Oxygen on Macrophage Response to Leishmania Infection
- Author
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Selma Giorgio, Fernanda Ramos Gadelha, Wagner Welber Arrais-Silva, Paulo Pinto Joazeiro, Marcelle Carolina Colhone, and Adriana Degrossoli
- Subjects
chemistry.chemical_classification ,Reactive oxygen species ,Ebselen ,Intracellular parasite ,Immunology ,General Medicine ,Biology ,Hypoxia (medical) ,Nitric oxide ,Cell biology ,Interleukin 10 ,chemistry.chemical_compound ,chemistry ,Interleukin 12 ,medicine ,Tumor necrosis factor alpha ,medicine.symptom - 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.
- Published
- 2011
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