Validation of proteins associated with pathological damage in human tuberculosis granulomas: study protocol

Thabo Mpotje; Jessica More; Kerishka Rajkumar-Bhugeloo; Denelle Moodley; Mohlopheni J Marakalala

doi:10.12688/wellcomeopenres.19226.1

Validation of proteins associated with pathological damage in human tuberculosis granulomas: study protocol

Wellcome Open Res. 2023 Mar 28:8:139. doi: 10.12688/wellcomeopenres.19226.1. eCollection 2023.

Authors

Thabo Mpotje^{1

2}, Jessica More^{1

2}, Kerishka Rajkumar-Bhugeloo^{1

2}, Denelle Moodley², Mohlopheni J Marakalala^{1

2

3}

Affiliations

¹ School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, KwaZulu-Natal, 4001, South Africa.
² Basic and Translational Science, Africa Health Research Institute, Durban, KwaZulu-Natal, 4001, South Africa.
³ Division of Infection and Immunity, University College London, London, England, UK.

Abstract

The presence of the Tuberculosis (TB) disease-causing pathogen, Mycobacterium Tuberculosis (Mtb), induces the development of a pathological feature termed granuloma, which the host uses to contain the bacteria. However, the granuloma may dissociate resulting in detrimental caseation of the lung. The disease contributes to a growing global burden of lung function challenges, warranting for more understanding of the TB-induced immunopathology. The current study aims to explore in detail host factors that drive pathological features of TB contributing to extensive lung tissue destruction. Lung tissue sections obtained from patients undergoing surgical resection will be processed and analyzed using histopathological assays including Immunohistochemistry, Immunofluorescence, Hematoxylin and Eosin staining and Laser Capture Microdissection. The findings will provide key host factors that associate with exacerbated lung immunopathology during TB.

Keywords: Host-Directed Therapies; Inflammation; Lung pathology; Mycobacterium tuberculosis; TB Granulomas.

Grants and funding

MJM is funded by the Wellcome Trust (grant#206751/A/17/Z) and Grand Challenges, an initiative of the Bill & Melinda Gates Foundation (grant #OPP1210776). TM is funded by the National Research Foundation Postdoctoral Fellowship. The work reported herein was also made possible through funding by the South African Medical Research Council through its Division of Research Capacity Development under the Mid-Career Scientist Programme (MJM) from funding received from the South African National Treasury. The content hereof is the sole responsibility of the authors and does not necessarily represent the official views of the funders.