title: Treatment in vitro with PPARα and PPARγ ligands drives M1-to-M2 polarization of macrophages from T. cruzi-infected mice.
abstract: Trypanosoma cruzi, the etiological agent of Chagas' disease, induces a persistent inflammatory response. Macrophages are a first line cell phenotype involved in the clearance of infection. Upon parasite uptake, these cells increase inflammatory mediators like NO, TNF-α, IL-1β and IL-6, leading to parasite killing. Although desired, inflammatory response perpetuation and exacerbation may lead to tissue damage. Peroxisome proliferator-activated receptors (PPARs) are ligand-dependent nuclear transcription factors that, besides regulating lipid and carbohydrate metabolism, have a significant anti-inflammatory effect. This is mediated through the interaction of the receptors with their ligands. PPARγ, one of the PPAR isoforms, has been implicated in macrophage polarization from M1, the classically activated phenotype, to M2, the alternatively activated phenotype, in different models of metabolic disorders and infection. In this study, we show for the first time that, besides PPARγ, PPARα is also involved in the in vitro polarization of macrophages isolated from T. cruzi-infected mice. Polarization was evidenced by a decrease in the expression of NOS2 and proinflammatory cytokines and the increase in M2 markers like Arginase I, Ym1, mannose receptor and TGF-β. Besides, macrophage phagocytic activity was significantly enhanced, leading to increased parasite load. We suggest that modulation of the inflammatory response by both PPARs might be due, at least in part, to a change in the profile of inflammatory macrophages. The potential use of PPAR agonists as modulators of overt inflammatory response during the course of Chagas' disease deserves further investigation.
authors.affiliation: Instituto de Investigaciones en Microbiología y Parasitología Médica (IMPaM-UBA, CONICET), Buenos Aires, Argentina.
authors.forename: Federico
authors.initials: F
authors.lastname: Penas
authors.affiliation: Instituto de Investigaciones en Microbiología y Parasitología Médica (IMPaM-UBA, CONICET), Buenos Aires, Argentina.
authors.forename: Gerardo A
authors.initials: GA
authors.lastname: Mirkin
authors.affiliation: Instituto de Investigaciones en Microbiología y Parasitología Médica (IMPaM-UBA, CONICET), Buenos Aires, Argentina.
authors.forename: Marcela
authors.initials: M
authors.lastname: Vera
authors.affiliation: Instituto de Investigaciones en Microbiología y Parasitología Médica (IMPaM-UBA, CONICET), Buenos Aires, Argentina.
authors.forename: Ágata
authors.initials: Á
authors.lastname: Cevey
authors.affiliation: Instituto de Investigaciones en Microbiología y Parasitología Médica (IMPaM-UBA, CONICET), Buenos Aires, Argentina.
authors.forename: Cintia D
authors.initials: CD
authors.lastname: González
authors.affiliation: Instituto de Investigaciones en Microbiología y Parasitología Médica (IMPaM-UBA, CONICET), Buenos Aires, Argentina.
authors.forename: Marisa I
authors.initials: MI
authors.lastname: Gómez
authors.affiliation: Centro de Estudios Farmacológicos y Botánicos (CEFyBO-UBA, CONICET), Buenos Aires, Argentina.
authors.forename: María Elena
authors.initials: ME
authors.lastname: Sales
authors.affiliation: Instituto de Investigaciones en Microbiología y Parasitología Médica (IMPaM-UBA, CONICET), Buenos Aires, Argentina. Electronic address: noragoren@hotmail.com.
authors.forename: Nora B
authors.initials: NB
authors.lastname: Goren
mesh_terms: D000818:Animals; D001119:Arginase / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D002478:Cells, Cultured; D014355:Chagas Disease / Q000235:genetics / Q000378:metabolism* / Q000469:parasitology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D054884:Host-Pathogen Interactions; D018836:Inflammation Mediators / Q000378:metabolism; D037102:Lectins / Q000235:genetics / Q000378:metabolism; D008024:Ligands; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000145:classification / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008807:Mice, Inbred BALB C; D008856:Microscopy, Fluorescence; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism*; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism*; D010587:Phagocytosis / Q000187:drug effects; D015230:Prostaglandin D2 / Q000031:analogs & derivatives / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D014349:Trypanosoma cruzi / Q000502:physiology; D001619:beta-N-Acetylhexosaminidases / Q000235:genetics / Q000378:metabolism
chemical_list: C477819:15-deoxyprostaglandin J2; D016207:Cytokines; D018836:Inflammation Mediators; D037102:Lectins; D008024:Ligands; D047493:PPAR alpha; D047495:PPAR gamma; D011743:Pyrimidines; D016212:Transforming Growth Factor beta; C006253:pirinixic acid; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C429541:Chil3 protein, mouse; D001619:beta-N-Acetylhexosaminidases; C544448:Arg1 protein, mouse; D001119:Arginase; D015230:Prostaglandin D2
keywords: Inflammatory mediators; Macrophage polarization; PPAR; Trypanosoma cruzi