Increased mortality in CD43-deficient mice during sepsis

• Type of Material: Article
• Authors: Katherine T. Fay, Emory University; Deena B. Chihade, Emory University; Ching-Wen Chen, Emory University; Nathan J. Klingensmith, Emory University; John D. Lyons, Emory University; Kimberly Ramonell, Emory University; Zhe Liang, Emory University; Craig Coopersmith, Emory University; Mandy Ford, Emory University
• Language: English
• Date: 2018-09-18
• Publisher: Public Library of Science
• Publication Version: Final Published Version
• Copyright Statement: © 2018 Fay et al.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1371/journal.pone.0202656
• Title of Journal or Parent Work: PLoS ONE
• ISSN: 1932-6203
• Volume: 13
• Issue: 9
• Start Page: e0202656
• End Page: e0202656
• Grant/Funding Information: The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.; This work was supported by funding from the National Institutes of Health (GM104323, GM109779, and GM113228 to MLF and CMC; and GM072808 and GM095442 to CMC).
• Keywords: IMMUNOSUPPRESSION; DEPLETION; INFLAMMATION; TH1/TH2; SEPTIC SHOCK; Science & Technology; Science & Technology - Other Topics; POLYMICROBIAL SEPSIS; CD43; APOPTOTIC CELL-DEATH; TRAUMA; Multidisciplinary Sciences; IMMUNITY
• Research Categories: Health Sciences, Medicine and Surgery; Health Sciences, Immunology; Biology, Cell

Abstract

CD43 is a large transmembrane protein involved in T cell activation. Previous studies of CD43-/-mice in viral models have demonstrated a role for CD43 in Th1/Th2 skewing, activation of Foxp3+ Treg, and T cell apoptosis. However, the role of CD43 during sepsis has never been tested. Thus, we interrogated the role of CD43 during sepsis using a murine cecal ligation and puncture (CLP) model, and found that CD43-/-mice demonstrated significantly worsened mortality compared to B6 mice following CLP. Phenotypic analysis of splenocytes isolated 24 h after septic insult revealed significantly increased apoptosis of central memory cells in both CD4+and CD8+T cell compartments in CD43-/-septic mice compared to WT septic mice. Furthermore, CD43-/-septic mice exhibited a prominent Th2 skewing following sepsis relative to WT septic mice, as evidenced by a significant decrease in the frequency of IL-2+CXCR3+TH1 cells as a significant increase in the frequency of IL-4+CCR4+TH2 cells. Finally, septic CD43-/-animals contained significantly fewer CD25+Foxp3+TRegcells as compared to WT septic animals. Importantly, depleting CD25+Treg eliminated the increased mortality observed in CD43-/-mice. Taken together, these data demonstrate an important role of CD43 in modulating immune dysregulation and mortality following sepsis.