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HOST-MICROBIOME INTERACTIONS AND REGULATION OF THE IMMUNE SYSTEM

Alvarez Contreras, Carlos Alberto
http://orcid.org/0000-0002-8652-9284
http://rave.ohiolink.edu/etdc/view?acc_num=case1600446008947681

Abstract Details

2021, Doctor of Philosophy, Case Western Reserve University, Pathology.
Multifactorial diseases such as diabetes, allergy and asthma, inflammatory bowel disease and neurodegenerative disorders have increased in recent years. Genetic predisposition is unable to fully account for this sudden increase, yet our environment is a factor that has seem similar dramatic changes even in the last 100 years. It has since become apparent that the gene pool of endogenous microbes that populate our bodies might be more susceptible to these changes due to their shorter life span and generation turnover. Thus, examination of the microbiome has become a major focus in the hopes of identifying underlying changes in the microbiome which may give rise to or be compounded due to disease. Study of these interactions have revealed the involvement of the microbiome in many functions ranging from processing of nutrients, neuronal and immune system development. The host immune interactions with gut commensal microbes have demonstrated their importance in establishing tolerance and maintenance of homeostasis. Here, we utilized the capsular polysaccharide PSA produced by the gut commensal Bacteroides fragilis to better understand the impact on the host immune system locally and systemically. Prior work established that PSA is endocytosed, processed and presented by APCs to CD4+ T cells via MHCII molecules. This exposure lead to the expansion of a population of C45Rblow effector memory (Tem) cells capable of protecting from induction of inflammation. This protection was shown to be IL-10 dependent, the source of which was endogenous Tregs and not the PSA expanded cells. Through in vitro co-culture experiments with regulatory T cells, we demonstrated a novel T cell communication axis by which Tem cells secrete IL-2 and IL-4 to synergistically stimulate IL-10 production by Tregs. Furthermore, we demonstrated that PSA exposure results in potent interferon response, which results in the upregulation of immune-regulatory markers. These markers were primarily found in the gut associated lymphoid tissue, providing an example by which commensal microbiota exposure can directly impact the immune cell population. Understanding how the host-microbiome interactions can impact the immune response can help in the treatment development and therapeutics for multiple inflammatory diseases.
Brian Cobb, PhD (Advisor)
Booki Min, DVM, PhD (Committee Chair)
Kristie Ross, MD (Committee Member)
Pushpa Pandiyan, PhD (Committee Member)
Clive Hamlin, PhD (Committee Member)
125 p.
Immunology
Immunology; Microbiome; PSA; Polysaccharide A; T cells; Host-Microbiome; Bacteroides Fragilis; Interferon Responsive Genes

Recommended Citations

Citations

  • Alvarez Contreras, C. A. (2021). HOST-MICROBIOME INTERACTIONS AND REGULATION OF THE IMMUNE SYSTEM [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1600446008947681

    APA Style (7th edition)

  • Alvarez Contreras, Carlos. HOST-MICROBIOME INTERACTIONS AND REGULATION OF THE IMMUNE SYSTEM . 2021. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1600446008947681.

    MLA Style (8th edition)

  • Alvarez Contreras, Carlos. "HOST-MICROBIOME INTERACTIONS AND REGULATION OF THE IMMUNE SYSTEM ." Doctoral dissertation, Case Western Reserve University, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=case1600446008947681

    Chicago Manual of Style (17th edition)

case1600446008947681
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