title: The class A scavenger receptor, macrophage receptor with collagenous structure, is the major phagocytic receptor for Clostridium sordellii expressed by human decidual macrophages.
abstract: Clostridium sordellii is an emerging pathogen associated with highly lethal female reproductive tract infections following childbirth, abortion, or cervical instrumentation. Gaps in our understanding of the pathogenesis of C. sordellii infections present major challenges to the development of better preventive and therapeutic strategies against this problem. We sought to determine the mechanisms whereby uterine decidual macrophages phagocytose this bacterium and tested the hypothesis that human decidual macrophages use class A scavenger receptors to internalize unopsonized C. sordellii. In vitro phagocytosis assays with human decidual macrophages incubated with pharmacological inhibitors of class A scavenger receptors (fucoidan, polyinosinic acid, and dextran sulfate) revealed a role for these receptors in C. sordellii phagocytosis. Soluble macrophage receptor with collagenous structure (MARCO) receptor prevented C. sordellii internalization, suggesting that MARCO is an important class A scavenger receptor in decidual macrophage phagocytosis of this microbe. Peritoneal macrophages from MARCO-deficient mice, but not wild-type or scavenger receptor AI/II-deficient mice, showed impaired C. sordellii phagocytosis. MARCO-null mice were more susceptible to death from C. sordellii uterine infection than wild-type mice and exhibited impaired clearance of this bacterium from the infected uterus. Thus, MARCO is an important phagocytic receptor used by human and mouse macrophages to clear C. sordellii from the infected uterus.
authors.affiliation: Molecular, Cellular, and Developmental Biology Graduate Program, Eastern Michigan University, Ypsilanti, MI 48197, USA.
authors.forename: Tennille
authors.initials: T
authors.lastname: Thelen
authors.forename: Yibai
authors.initials: Y
authors.lastname: Hao
authors.forename: Alexandra I
authors.initials: AI
authors.lastname: Medeiros
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Curtis
authors.forename: Carlos H
authors.initials: CH
authors.lastname: Serezani
authors.forename: Lester
authors.initials: L
authors.lastname: Kobzik
authors.forename: Lisa H
authors.initials: LH
authors.lastname: Harris
authors.forename: David M
authors.initials: DM
authors.lastname: Aronoff
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D003015:Clostridium Infections / Q000276:immunology*; D047989:Paraclostridium sordellii / Q000276:immunology; D003656:Decidua / Q000166:cytology / Q000276:immunology*; D005260:Female; D006801:Humans; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D018345:Mice, Knockout; D010587:Phagocytosis / Q000276:immunology; D011971:Receptors, Immunologic / Q000276:immunology* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055815:Young Adult
chemical_list: C490460:MARCO protein, human; D011971:Receptors, Immunologic
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