title: Resolvin D1 drives establishment of Leishmania amazonensis infection.
abstract: Previous studies have indicated that the balance between different eicosanoids reflect the intensity of the inflammatory profile in patients with tegumentary leishmaniasis. More recently, pro-resolution lipid mediators have been shown to play critical roles in dampening pathological inflammatory processes to reestablish homeostasis in a diverse range of experimental settings. Among these lipid mediator, resolvins from D series have been described as potent anti-inflammatory and immunomodulatory mediators, and its activities include inhibition of leukocyte chemotaxis and blockage production of proinflammatory cytokines, while increasing the expression of regulatory mediators. Whether resolvins play significant roles in establishment and persistence of Leishmania infection is currently unknown. We addressed this question in the current study by assessing circulating levels of D-series resolvins in tegumentary leishmaniasis patients presenting with localized or diffuse disease. We found heightened expression of resolvin D1 in diffuse cutaneous leishmaniasis which was correlated with expression profile of biomarkers associated with disease pathogenesis. Additional in vitro experiments using primary human macrophages indicated that resolvin D1 may promote intracellular Leishmania amazonensis replication through a mechanism associated with induction of heme oxygenase-1. These results suggest that targeting resolvin D1 could serve as potential strategy for host directed therapy in diffuse cutaneous leishmaniasis.
authors.affiliation: Instituto Gonçalo Moniz, Fundação Oswaldo Cruz (FIOCRUZ), Salvador, Brazil.|Universidade Federal da Bahia, Salvador, Brazil.
authors.forename: Hayna
authors.initials: H
authors.lastname: Malta-Santos
authors.affiliation: Instituto Gonçalo Moniz, Fundação Oswaldo Cruz (FIOCRUZ), Salvador, Brazil.|Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Fundação José Silveira, Salvador, Brazil.
authors.forename: Bruno B
authors.initials: BB
authors.lastname: Andrade
authors.affiliation: Instituto Gonçalo Moniz, Fundação Oswaldo Cruz (FIOCRUZ), Salvador, Brazil.
authors.forename: Dalila L
authors.initials: DL
authors.lastname: Zanette
authors.affiliation: Instituto Gonçalo Moniz, Fundação Oswaldo Cruz (FIOCRUZ), Salvador, Brazil.
authors.forename: Jackson M
authors.initials: JM
authors.lastname: Costa
authors.affiliation: Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.
authors.forename: Patrícia T
authors.initials: PT
authors.lastname: Bozza
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho (IBCCF), Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Christianne
authors.initials: C
authors.lastname: Bandeira-Melo
authors.affiliation: Instituto Gonçalo Moniz, Fundação Oswaldo Cruz (FIOCRUZ), Salvador, Brazil.|Universidade Federal da Bahia, Salvador, Brazil.
authors.forename: Aldina
authors.initials: A
authors.lastname: Barral
authors.affiliation: Instituto Gonçalo Moniz, Fundação Oswaldo Cruz (FIOCRUZ), Salvador, Brazil.|Universidade Federal da Bahia, Salvador, Brazil.
authors.forename: Jaqueline
authors.initials: J
authors.lastname: França-Costa
authors.affiliation: Instituto Gonçalo Moniz, Fundação Oswaldo Cruz (FIOCRUZ), Salvador, Brazil.|Universidade Federal da Bahia, Salvador, Brazil.
authors.forename: Valéria M
authors.initials: VM
authors.lastname: Borges
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D002648:Child; D004281:Docosahexaenoic Acids / Q000097:blood*; D005260:Female; D006801:Humans; D007891:Leishmania; D007896:Leishmaniasis / Q000097:blood*; D008264:Macrophages / Q000378:metabolism / Q000469:parasitology*; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D015415:Biomarkers; C518399:resolvin D1; D004281:Docosahexaenoic Acids