title: Human classical monocytes control the intracellular stage of Leishmania braziliensis by reactive oxygen species.
abstract: Leishmania braziliensis are intracellular parasites that cause unique clinical forms of cutaneous leishmaniasis. Previous studies with other leishmania species demonstrated that reactive oxygen species (ROS) control promastigotes, the infective stage of the parasite, but not the amastigote form that exists in the mammalian host. Here we show that ROS inhibits growth of L. braziliensis amastigotes in resting monocytes, and that classical monocytes are primarily responsible for this control. ROS, but not nitric oxide, also contributed to killing of L. braziliensis by IFN-γ activated monocytes. Furthermore, by gene expression profiling of human lesions we found greater expression of genes associated with ROS, but not nitric oxide, compared to normal skin. This study shows that ROS are important for control of L. braziliensis both at the initial stages of infection, as well as at later time points, and highlights that monocyte subsets may play different roles during leishmaniasis.
authors.affiliation: Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Fernanda O
authors.initials: FO
authors.lastname: Novais
authors.forename: Ba T
authors.initials: BT
authors.lastname: Nguyen
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Beiting
authors.forename: Lucas P
authors.initials: LP
authors.lastname: Carvalho
authors.forename: Nelson D
authors.initials: ND
authors.lastname: Glennie
authors.forename: Sara
authors.initials: S
authors.lastname: Passos
authors.forename: Edgar M
authors.initials: EM
authors.lastname: Carvalho
authors.forename: Phillip
authors.initials: P
authors.lastname: Scott
mesh_terms: D000818:Animals; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D006801:Humans; D007892:Leishmania braziliensis / Q000502:physiology*; D016773:Leishmaniasis, Cutaneous / Q000378:metabolism / Q000517:prevention & control*; D009000:Monocytes / Q000378:metabolism / Q000469:parasitology*; D009569:Nitric Oxide / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010414:Pennsylvania; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; D009569:Nitric Oxide
keywords: Leishmania braziliensis; amastigotes; human monocytes; nitric oxide; reactive oxygen species