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Phagocytosis by Fibrocytes as a Mechanism to Decrease Bacterial Burden and Increase Survival in Sepsis

Collins, Dalis*; Fry, Christopher; Moore, Bethany B.; Nemzek, Jean A.

doi: 10.1097/SHK.0000000000001161
Basic Science Aspects
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ABSTRACT Fibrocytes are unique cells with innate and adaptive immune functions, but these mechanisms have not been fully explored. The aim of this study was to explain the mechanism by which adoptive transfer of exogenous fibrocytes improved bacterial clearance and increased sepsis survival. Initial flow cytometry-based, in vitro assays demonstrated phagocytosis by fibrocytes and intracellular bacterial killing was confirmed by direct plating of cell lysates after exposure to live bacteria. Intravenous adoptive transfer of fibrocytes at the time of cecal ligation and puncture (CLP) or 2 h after CLP in mice increased survivability. Decreased intraperitoneal bacterial burden was also observed. Quantification of peritoneal cell populations using flow cytometry demonstrated transferred and endogenous fibrocytes were significantly increased after CLP, while macrophage and neutrophil numbers were unchanged. To determine the impact in vivo, fluorescently labeled, killed bacteria were injected i.p. into mice 10 h after CLP or sham surgery ± adoptive transfer. Two hours later, flow cytometry of peritoneal cell populations after CLP alone revealed increased phagocytosis by macrophages, neutrophils, and endogenous fibrocytes. Transferred fibrocytes had significantly increased phagocytic activity in the septic peritoneum compared with sham and greater activity than any other cell type. Therefore, adoptive transfer may enhance bacterial clearance in early sepsis through the cumulative effects of endogenous and transferred fibrocytes rather than modulating the function of other endogenous phagocytes. Direct phagocytic activity coupled with previously described influences on T cell responses may explain the benefits of fibrocyte transfer in sepsis.

*Center for Comparative Medicine, Baylor College of Medicine, Houston, TX

Unit for Laboratory Animal Medicine, University of Michigan, Ann Arbor, MI

Division of Pulmonary and Critical Care Medicine in the Department of Internal Medicine and Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI

Address reprint requests to Dr. Jean A. Nemzek, DVM, MS, DACVS, Unit for Laboratory Animal Medicine, University of Michigan, Ann Arbor, MI 48109. E-mail: jnemzek@umich.edu; Co-correspondence: Dalis Collins, DVM, DACLAM, Center for Comparative Medicine, Baylor College of Medicine, Houston, TX 77030. E-mail: dcollins@bcm.edu

Received 22 January, 2018

Revised 7 February, 2018

Accepted 10 April, 2018

The UM Flow Cytometry Core is supported by the National Cancer Institute of the National Institutes of Health under award number P30CA046592. The experimental work was supported by NIH Grants HL108196 (JN), GM112799 (JN) and AI117229 (BBM).

The authors report no conflicts of interest.

© 2019 by the Shock Society