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Treatment of Staphylococcus aureus Infection by Hematopoietic Stem and Progenitor Cells and the Role of Chemokine C-C Motif Receptor 6 in Wound Healing.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Treatment of Staphylococcus aureus Infection by Hematopoietic Stem and Progenitor Cells and the Role of Chemokine C-C Motif Receptor 6 in Wound Healing./
Author:	Anderson, Leif Stefan.
Published:	Ann Arbor : ProQuest Dissertations & Theses, : 2019,
Description:	78 p.
Notes:	Source: Dissertations Abstracts International, Volume: 80-09, Section: B.
Contained By:	Dissertations Abstracts International80-09B.
Subject:	Bioengineering. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=13420794
ISBN:	9780438931244

Treatment of Staphylococcus aureus Infection by Hematopoietic Stem and Progenitor Cells and the Role of Chemokine C-C Motif Receptor 6 in Wound Healing.
Anderson, Leif Stefan.

Treatment of Staphylococcus aureus Infection by Hematopoietic Stem and Progenitor Cells and the Role of Chemokine C-C Motif Receptor 6 in Wound Healing. - Ann Arbor : ProQuest Dissertations & Theses, 2019 - 78 p.

Source: Dissertations Abstracts International, Volume: 80-09, Section: B.

Thesis (Ph.D.)--University of California, Davis, 2019.

This item must not be sold to any third party vendors.

Delayed and chronic wounds, including diabetic and infected wounds, are an enormous burden on the healthcare system. Wound healing requires coordinated action between tissue resident and recruited immune cells. Resident keratinocytes, fibroblasts, and endothelial cells respond to tissue damage and pathogens by secreting proteases that digest extracellular matrix, growth factors to stimulate cell proliferation, and cytokines and chemokines that recruit circulating leukocytes. Neutrophils clear bacterial pathogens and macrophages phagocytose apoptotic cells and debris, as well as produce factors that promote wound closure. Skin resident γδ T cells produce factors that promote keratinocyte proliferation and wound re-epithelialization, and trafficking γδT cells participate in epithelial tissue repair, as removal of these cells results in impaired wound healing in mouse models. The chemokine receptor CCR6 is expressed on monocytes, T cells, and dendritic cells and, recently it was reported that CCR6+ γδ T cells regulate repair of corneal and diabetic wounds, which motivated us to examine mechanisms of leukocyte recruitment and repair of skin wounds. A four-day delay in wound closure was observed in CCR6-/- compared to wild-type C57BL/6 mice. Day 5 wounds of CCR6-/- mice contained 60% fewer γδ T cells and 75% fewer Vγ4 T cells, and 20-fold more IL-17A and 8-fold less FGF2 expression was measured in CCR6-/- wounds compared to wild-type wounds. Adoptive transfer of wild-type γδ T cells in CCR6-/- mice effectively restored normal healing that was dependent upon their trafficking into the wound. We conclude that CCR6 on γδ T cells governs emigration and participation in healing of cutaneous wounds. This is the first demonstration that CCR6+ γδ T cells rapidly migrate to cutaneous wounds where they play a critical role in restoring optimal skin healing. Wounds serve as a susceptible entrance for pathogens to infect a host. Staphylococcus aureus (S. aureus) is a particularly dangerous gram-positive bacterium and is responsible for the majority of skin and soft tissue infections in the United States of America. With incidence rates of S. aureus infection on the rise, there is a demand for additional research into its pathogenicity. Animal models of infectious disease advance our understanding of the host-pathogen response and lead to the development of effective therapeutics. Neutrophils play a primary role in the innate immune response that controls S. aureus infections by forming an abscess to wall off the infection and facilitate bacterial clearance; the number of neutrophils that infiltrate an S. aureus skin infection often correlates with disease outcome. Increasing neutrophil numbers in a wound is a potential therapeutic technique to treat S. aureus infection. Hematopoietic stem and progenitor cell (HSPC) traffic to an infected wound and undergo granulopoiesis, providing a local source of bactericidal neutrophils. Herein, we explore HSPC delivery as a cellular therapy for lethal S. aureus infection in an immunodeficient mouse model. Following wounding, infection, and HSPC transfer in an immunodeficient MyD88-/- mice, 80% of untreated mice succumbed to infection within 7 days of wounding and infection. In contrast, 80% of the mice that received injection of HSPC into their wounds survived over the same interval. Survival in WT HSPC recipients correlated with a significant reduction in bacterial burden in the kidneys by 72 hours post-infection, suggesting that HSPCs play a critical role in preventing bacterial dissemination. HSPC were found to utilize IL-1 signaling to contain S. aureus infection in studies using donor HSPCs deficient in IL-1β or IL-1R instead of HSPC from WT mice. We conclude that γδ T cells play an important role in wound healing and HSPC transfer is a viable strategy for resolution of S. aureus infection.

ISBN: 9780438931244Subjects--Topical Terms:

657580
Bioengineering.

Treatment of Staphylococcus aureus Infection by Hematopoietic Stem and Progenitor Cells and the Role of Chemokine C-C Motif Receptor 6 in Wound Healing.
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