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Talib's Dissertation Final 04-17-18.pdf (1.85 MB)

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Kruppel-like factor 2: A regulator of macrophage-mediated innate immune response against Staphylococcus aureus biofilm.

ALBOSLEMY, TALIB
http://orcid.org/0000-0002-5361-372X
http://rave.ohiolink.edu/etdc/view?acc_num=kent1523544938448141

Abstract Details

2018, PHD, Kent State University, College of Arts and Sciences / School of Biomedical Sciences.
Complications arising from cutaneous and soft tissue infections with Staphylococcus aureus (S. aureus) are a major clinical problem due to the high incidence of these infections and the widespread emergence of antibiotic-resistant bacterial strains. In particular, S. aureus infection involving the formation of biofilm is clinically challenging due to antibiotic resistance and immune evasive characteristics of biofilm-associated infection. Accumulating evidences support that macrophages associated with S. aureus biofilms have decreased secretion of cytokines and chemokines, which might have contributed to the impaired bactericidal activity. A series of recent studies have demonstrated that S. aureus biofilms skew macrophage polarization towards an anti-inflammatory phenotype that persists bacterial survival. However, the detailed mechanism underlying the evasion of macrophage-mediated innate immune response against S. aureus biofilm is poorly understood. The central hypothesis of this study is that S. aureus biofilm environment skews macrophage polarization toward the anti-inflammatory phenotype by interfering with a pattern recognition receptor (PRR)-dependent positive regulatory mechanism or aberrantly amplifying a negative regulatory mechanism of NF-kB activation. In this study, using an in vitro model of murine macrophages exposed to the secreted factors from S. aureus biofilm, we have determined the impact of the S. aureus biofilms on macrophage-mediated innate immune response and elucidated its associated signaling mechanism. The major finding of this study is that S. aureus biofilm environment associated with alpha toxin skews macrophage polarization toward the anti-inflammatory phenotype by aberrantly increasing the expression of krupper-like factor 2 (KLF2) in macrophages, which in turn negatively regulate the activation of NF-kB pathways for host innate immune responses. Our study provides an important insight into the mechanism by which S. aureus biofilm impair macrophage-mediated innate immune defense functions and is the first to identify KLF2 in macrophage as a molecular target by S. aureus biofilm to evade innate immune attack by macrophages. Understanding the nature of host-microbial interactions, in particular in the context of the mechanisms used by S. aureus biofilm to evade host innate immune defense, is the key to develop an effective immunotherapy for combating infectious diseases. Our study provides a new opportunity for immunotherapy for targeting macrophage polarization toward the anti-biofilm phenotype by targeting KLF2 and its associated signalling in macrophages against S. aureus biofilm infection.
Min-HO Kim (Advisor)
122 p.
Biomedical Research
Staphylococcus aureus; Biofilms; Macrophage; Inflammation; innate immune response; KLF-2

Recommended Citations

Citations

  • ALBOSLEMY, T. (2018). Kruppel-like factor 2: A regulator of macrophage-mediated innate immune response against Staphylococcus aureus biofilm. [Doctoral dissertation, Kent State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=kent1523544938448141

    APA Style (7th edition)

  • ALBOSLEMY, TALIB. Kruppel-like factor 2: A regulator of macrophage-mediated innate immune response against Staphylococcus aureus biofilm. 2018. Kent State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=kent1523544938448141.

    MLA Style (8th edition)

  • ALBOSLEMY, TALIB. "Kruppel-like factor 2: A regulator of macrophage-mediated innate immune response against Staphylococcus aureus biofilm." Doctoral dissertation, Kent State University, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=kent1523544938448141

    Chicago Manual of Style (17th edition)

kent1523544938448141
227
© 2018, some rights reserved.Creative Commons License Kruppel-like factor 2: A regulator of macrophage-mediated innate immune response against Staphylococcus aureus biofilm. by TALIB ALBOSLEMY is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. Based on a work at etd.ohiolink.edu.
This open access ETD is published by Kent State University and OhioLINK.
Release 3.2.12