title: Infection with Leishmania major induces a cellular stress response in macrophages.
abstract: We investigated early cellular responses induced by infection with Leishmania major in macrophages from resistant C57/BL6 mice. Infection increased production of reactive oxygen species by resident, but not inflammatory peritoneal macrophages. In addition, infection increased activation of stress-activated protein kinases/c-Jun N-terminal kinases (SAPK/JNK) in resident, but not in inflammatory peritoneal macrophages. Infection also increased expression of membrane and soluble FasL, but infected macrophages remained viable after 48 h. Infection increased secretion of cytokines/chemokines TNF-α, IL-6, TIMP-1, IL-1RA, G-CSF, TREM, KC, MIP-1α, MIP-1β, MCP-1, and MIP-2 in resident macrophages. Addition of antioxidants deferoxamine and N-acetylcysteine reduced ROS generation and JNK activation. Addition of antioxidants or JNK inhibitor SP600125 reduced secretion of KC. Furthermore, treatment with antioxidants or JNK inhibitor also reduced intracellular parasite replication. These results indicated that infection triggers a rapid cellular stress response in resident macrophages which induces proinflammatory signals, but is also involved in parasite survival and replication in host macrophages.
authors.affiliation: Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Alessandra A
authors.initials: AA
authors.lastname: Filardy
authors.affiliation: Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Ana Caroline
authors.initials: AC
authors.lastname: Costa-da-Silva
authors.affiliation: Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Carolina M
authors.initials: CM
authors.lastname: Koeller
authors.affiliation: Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Kamila
authors.initials: K
authors.lastname: Guimarães-Pinto
authors.affiliation: Laboratory of Parasitic Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Flávia L
authors.initials: FL
authors.lastname: Ribeiro-Gomes
authors.affiliation: Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Marcela F
authors.initials: MF
authors.lastname: Lopes
authors.affiliation: Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Norton
authors.initials: N
authors.lastname: Heise
authors.affiliation: Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Célio G
authors.initials: CG
authors.lastname: Freire-de-Lima
authors.affiliation: Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
authors.forename: Marise P
authors.initials: MP
authors.lastname: Nunes
authors.affiliation: Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: George A
authors.initials: GA
authors.lastname: DosReis
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D018925:Chemokines / Q000096:biosynthesis; D053222:Fas Ligand Protein / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D018320:Leishmania major / Q000187:drug effects / Q000254:growth & development / Q000502:physiology*; D016773:Leishmaniasis, Cutaneous / Q000469:parasitology* / Q000473:pathology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology / Q000469:parasitology* / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010271:Parasites / Q000187:drug effects / Q000254:growth & development / Q000502:physiology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D013312:Stress, Physiological / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000975:Antioxidants; D018925:Chemokines; D053222:Fas Ligand Protein; D047428:Protein Kinase Inhibitors; D017382:Reactive Oxygen Species; D048031:JNK Mitogen-Activated Protein Kinases