Bacterial Killing Activity of Polymorphonuclear Myeloid-Derived Suppressor Cells Isolated From Tumor-Bearing Dogs
Polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) are implicated in the progression and outcome of a variety of pathological states, from cancer to infection. Our previous work has identified three antimicrobial peptides differentially expressed by PMN-MDSCs compared to conventional neu...
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doaj-e4e140b93e4f40a88131d4726bc59a002020-11-25T02:28:18ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-10-011010.3389/fimmu.2019.02371488796Bacterial Killing Activity of Polymorphonuclear Myeloid-Derived Suppressor Cells Isolated From Tumor-Bearing DogsSabina I. Hlavaty0Yu-Mei Chang1Rachel P. Orth2Mark Goulian3Paul J. Planet4Paul J. Planet5Douglas H. Thamm6Jennifer A. Punt7Oliver A. Garden8Garden Immune Regulation Laboratory, Department of Clinical Sciences and Advanced Medicine, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, United StatesResearch Support Office, Royal Veterinary College, London, United KingdomSchool of Arts and Sciences, University of Pennsylvania, Philadelphia, PA, United StatesDepartment of Biology, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA, United StatesDepartment of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United StatesPediatric Infectious Disease Division, Children's Hospital of Philadelphia, Philadelphia, PA, United StatesFlint Animal Cancer Center, Department of Clinical Sciences, Colorado State University, Fort Collins, CO, United StatesDepartment of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, United StatesGarden Immune Regulation Laboratory, Department of Clinical Sciences and Advanced Medicine, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, United StatesPolymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) are implicated in the progression and outcome of a variety of pathological states, from cancer to infection. Our previous work has identified three antimicrobial peptides differentially expressed by PMN-MDSCs compared to conventional neutrophils isolated from dogs, mice, and human patients with cancer. We therefore hypothesized that PMN-MDSCs in dogs with cancer possess antimicrobial activity. In the current work, we observed that exposure of PMN-MDSCs to Gram-negative bacteria (Escherichia coli) increased the expression of reactive oxygen species by the PMN-MDSCs, indicating that they are capable of initiating an anti-microbial response. Electron microscopy revealed that the PMN-MDSCs phagocytosed Gram-negative and Gram-positive (Staphylococcus aureus) bacterial species. Lysis of bacteria within some of the PMN-MDSCs suggested bactericidal activity, which was confirmed by the recovery of significantly lower numbers of bacteria of both species following exposure to PMN-MDSCs isolated from tumor-bearing dogs. Our data therefore indicate that PMN-MDSCs isolated from dogs with cancer, in common with PMNs, have phagocytic and bactericidal activity. This nexus of immunosuppressive and antimicrobial activity reveals a hitherto unrecognized function of MDSCs.https://www.frontiersin.org/article/10.3389/fimmu.2019.02371/fullMDSCPMN-MDSCG-MDSCcaninecancerbactericidal |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Sabina I. Hlavaty Yu-Mei Chang Rachel P. Orth Mark Goulian Paul J. Planet Paul J. Planet Douglas H. Thamm Jennifer A. Punt Oliver A. Garden |
spellingShingle |
Sabina I. Hlavaty Yu-Mei Chang Rachel P. Orth Mark Goulian Paul J. Planet Paul J. Planet Douglas H. Thamm Jennifer A. Punt Oliver A. Garden Bacterial Killing Activity of Polymorphonuclear Myeloid-Derived Suppressor Cells Isolated From Tumor-Bearing Dogs Frontiers in Immunology MDSC PMN-MDSC G-MDSC canine cancer bactericidal |
author_facet |
Sabina I. Hlavaty Yu-Mei Chang Rachel P. Orth Mark Goulian Paul J. Planet Paul J. Planet Douglas H. Thamm Jennifer A. Punt Oliver A. Garden |
author_sort |
Sabina I. Hlavaty |
title |
Bacterial Killing Activity of Polymorphonuclear Myeloid-Derived Suppressor Cells Isolated From Tumor-Bearing Dogs |
title_short |
Bacterial Killing Activity of Polymorphonuclear Myeloid-Derived Suppressor Cells Isolated From Tumor-Bearing Dogs |
title_full |
Bacterial Killing Activity of Polymorphonuclear Myeloid-Derived Suppressor Cells Isolated From Tumor-Bearing Dogs |
title_fullStr |
Bacterial Killing Activity of Polymorphonuclear Myeloid-Derived Suppressor Cells Isolated From Tumor-Bearing Dogs |
title_full_unstemmed |
Bacterial Killing Activity of Polymorphonuclear Myeloid-Derived Suppressor Cells Isolated From Tumor-Bearing Dogs |
title_sort |
bacterial killing activity of polymorphonuclear myeloid-derived suppressor cells isolated from tumor-bearing dogs |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2019-10-01 |
description |
Polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) are implicated in the progression and outcome of a variety of pathological states, from cancer to infection. Our previous work has identified three antimicrobial peptides differentially expressed by PMN-MDSCs compared to conventional neutrophils isolated from dogs, mice, and human patients with cancer. We therefore hypothesized that PMN-MDSCs in dogs with cancer possess antimicrobial activity. In the current work, we observed that exposure of PMN-MDSCs to Gram-negative bacteria (Escherichia coli) increased the expression of reactive oxygen species by the PMN-MDSCs, indicating that they are capable of initiating an anti-microbial response. Electron microscopy revealed that the PMN-MDSCs phagocytosed Gram-negative and Gram-positive (Staphylococcus aureus) bacterial species. Lysis of bacteria within some of the PMN-MDSCs suggested bactericidal activity, which was confirmed by the recovery of significantly lower numbers of bacteria of both species following exposure to PMN-MDSCs isolated from tumor-bearing dogs. Our data therefore indicate that PMN-MDSCs isolated from dogs with cancer, in common with PMNs, have phagocytic and bactericidal activity. This nexus of immunosuppressive and antimicrobial activity reveals a hitherto unrecognized function of MDSCs. |
topic |
MDSC PMN-MDSC G-MDSC canine cancer bactericidal |
url |
https://www.frontiersin.org/article/10.3389/fimmu.2019.02371/full |
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