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.
Footnotes
This work was supported by National Institutes of Health Grants HD057176 (to D.M.A.), ES11008 (to L.K.), and HL056309 (to J.L.C.). Support for nonanimal portions of this work was provided by a Doris Duke Charitable Fund Clinical Scientist Development Award (to D.M.A.).
Abbreviations used in this paper:
- AcLDL
- acetylated low-density lipoprotein
- CASR
- class A scavenger receptor
- CBSR
- class B scavenger receptor
- ChdSO4
- chondroitan sulfate
- DM
- decidual macrophage
- DxSO4
- dextran sulfate
- KO
- knockout
- MARCO
- macrophage receptor with collagenous structure
- PI
- phagocytic index
- poly(C)
- polycytidylic acid
- poly(I)
- polyinosinic acid
- RFU
- relative fluorescence unit
- SCARA-5
- scavenger receptor A5
- sMARCO
- soluble MARCO
- SR-AI/II
- scavenger receptor AI and AII
- SRCL
- scavenger receptor with C-type lectin
- WT
- wild type.
- Received March 26, 2010.
- Accepted July 20, 2010.
- Copyright © 2010 by The American Association of Immunologists, Inc.