Phenotypic characterization of B cells and serum cytokine responses during Tuberculosis and Type 2 Diabetes

Shabangu, Ayanda Noncedo (2019-12)

Thesis (MSc)--Stellenbosch University, 2019.

Thesis

ENGLISH ABSTRACT: Tuberculosis (TB) remains a world pandemic, claiming the lives of 1.7 million people in 2017. Several risk factors have been identified as key attributes to the development of TB, such as type 2 diabetes (T2D). Cellular function of immune cell types are altered in TB-T2D patients compared to TB patients, leaving the host vulnerable to increased Mycobacterium tuberculosis (Mtb) replication and enhanced disease severity. Emphasis has been placed on the role of T-cells and macrophages in TB-T2D comorbidity, however, B-cells also play a fundamental role in the adaptive immune response to TB. Since limited information is available on the frequency of B cells in TB in the context of T2D, we aimed to determine the frequencies of regulatory and killer B-cell, through the expression of the cell surface markers, FasL (CD178+) and IL-5Rα (CD125+). In addition, we investigate imbalances in host immune markers in healthy controls, T2D patients and TB patients with and without T2D. The immunological responses, including regulatory, memory and apoptotic B-cell function, are impaired in T2D, TB and TB-T2D patients at the initiation of TB treatment, and improve in TB and TB-T2D patients following two months into anti-TB treatment. In addition, markers associated with cell proliferation, cell development, chemotactic function, granuloma formation and monocyte recruitment are impaired, highlighting the need for effective T2D management in combating TB.

AFRIKAANSE OPSOMMING: Tuberkulose (TB) bly 'n wêreldpandemie wat die lewens van 1,7 miljoen mense in 2017 geëis het. Verskeie risikofaktore is geïdentifiseer as sleutelkenmerke vir die ontwikkeling van TB, soos tipe 2-diabetes (T2D). Die sellulêre funksie van immuunselle in TB-T2D-pasiënte is anders in vergelyking met TB-pasiënte, wat die gasheer kwesbaar maak vir verhoogde Mycobacterium tuberculosis (Mtb) replikasie en die erns van die siekte verhoog. Klem is gelê op die rol van T-selle en makrofage in die TB-T2D mede-morbiditeit. B-selle speel egter ook 'n fundamentele rol in die aanpasbare immuunrespons op TB. Aangesien beperkte inligting beskikbaar is oor die frekwensie van B-selle in TB in die konteks van T2D, het ons ten doel gehad om die frekwensies van regulatoriese en moordenaar B-selle te bepaal, deur die uitdrukking van die seloppervlakte-merkers, FasL (CD178+) en IL-5Rα (CD125+) te meet. Daarbenewens ondersoek ons wanbalanse in die gasheer immuunmerkers in gesonde kontroles, T2D-pasiënte en TB-pasiënte met en sonder T2D. Die immunologiese reaksies, insluitend regulatoriese, geheue en apoptotiese Bselfunksie, word aangetas in T2D-, TB- en TB-T2D-pasiënte voor die aanvang van TB behandeling, en verbeter in die TB- en TB-T2D-pasiënte na twee maande van TB behandeling. Verder word merkers wat verband hou met selproliferasie, selontwikkeling, chemotaktiese funksie, granuloomvorming en monosiet-werwing benadeel, wat die behoefte aan effektiewe T2D-bestuur in die bestryding van TB benadruk.

Please refer to this item in SUNScholar by using the following persistent URL: http://hdl.handle.net/10019.1/106939
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