title: CD163 favors Mycobacterium leprae survival and persistence by promoting anti-inflammatory pathways in lepromatous macrophages.
abstract: Lepromatous macrophages possess a regulatory phenotype that contributes to the immunosuppression observed in leprosy. CD163, a scavenger receptor that recognizes hemoglobin-haptoglobin complexes, is expressed at higher levels in lepromatous cells, although its functional role in leprosy is not yet established. We herein demonstrate that human lepromatous lesions are microenvironments rich in IDO⁺CD163⁺. Cells isolated from these lesions were CD68⁺IDO⁺CD163⁺ while higher levels of sCD163 in lepromatous sera positively correlated with IL-10 levels and IDO activity. Different Myco-bacterium leprae (ML) concentrations in healthy monocytes likewise revealed a positive correlation between increased concentrations of the mycobacteria and IDO, CD209, and CD163 expression. The regulatory phenotype in ML-stimulated monocytes was accompanied by increased TNF, IL-10, and TGF-β levels whereas IL-10 blockade reduced ML-induced CD163 expression. The CD163 blockade reduced ML uptake in human monocytes. ML uptake was higher in HEK293 cells transfected with the cDNA for CD163 than in untransfected cells. Simultaneously, increased CD163 expression in lepromatous cells seemed to be dependent on ML uptake, and contributed to augmented iron storage in lepromatous macrophages. Altogether, these results suggest that ML-induced CD163 expression modulates the host cell phenotype to create a favorable environment for myco-bacterial entry and survival.
authors.affiliation: Leprosy Laboratory, Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro, Brazil.
authors.forename: Danielle F
authors.initials: DF
authors.lastname: Moura
authors.forename: Katherine A
authors.initials: KA
authors.lastname: de Mattos
authors.forename: Thaís P
authors.initials: TP
authors.lastname: Amadeu
authors.forename: Priscila R
authors.initials: PR
authors.lastname: Andrade
authors.forename: Jorgenilce S
authors.initials: JS
authors.lastname: Sales
authors.forename: Verônica
authors.initials: V
authors.lastname: Schmitz
authors.forename: José Augusto C
authors.initials: JA
authors.lastname: Nery
authors.forename: Roberta O
authors.initials: RO
authors.lastname: Pinheiro
authors.forename: Euzenir N
authors.initials: EN
authors.lastname: Sarno
mesh_terms: D015703:Antigens, CD / Q000235:genetics / Q000276:immunology*; D015214:Antigens, Differentiation, Myelomonocytic / Q000235:genetics / Q000276:immunology*; D001706:Biopsy; D005434:Flow Cytometry; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology; D015440:Leprosy, Lepromatous / Q000276:immunology* / Q000382:microbiology* / Q000473:pathology; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology; D009166:Mycobacterium leprae / Q000276:immunology*; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000098902:CD163 Antigen; C576710:IDO1 protein, human; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D016753:Interleukin-10