TY - JOUR
T1 - Cellular architecture of spinal granulomas and the immunological response in tuberculosis patients coinfected with HIV
AU - Bhattacharya, Debapriya
AU - Danaviah, Siva
AU - Muema, Daniel M.
AU - Akilimali, Ngomu Akeem
AU - Moodley, Prashini
AU - Ndung'u, Thumbi
AU - Das, Gobardhan
N1 - Funding Information:
We would like to acknowledge the patients and their families, and the staff at King Dinuzulu Hospital. We gratefully acknowledge financial support by the National Research Foundation, the Howard Hughes Medical Institute and the Victor Daitz Foundation. TN holds the South Africa Research Chair in Systems Biology of HIV/AIDS. This work was also supported in part through the Sub-Saharan African Network for TB/HIV Research Excellence (SANTHE), a DELTAS Africa Initiative (grant # DEL-15-006). The DELTAS Africa Initiative is an independent funding scheme of the African Academy of Sciences (AAS)’s Alliance for Accelerating Excellence in Science in Africa (AESA) and supported by the New Partnership for Africa’s Development Planning and Coordinating Agency (NEPAD Agency) with funding from the Wellcome Trust (grant # 107752/Z/15/Z) and the UK government. Partly, this work is funded by DBT (BT/01/ CEIB/11/VI/05), India, and Indo-South African DBT grant (BT/ PR24544/MED/29/1217/2017) (DBT, India) funded to GD. The work was also partially funded by an Indo-South African SHIP Programme South African Medical Research Council (SAMRC) grant to TN. The views expressed in this publication are those of the author(s) and not necessarily those of AAS, NEPAD Agency, Wellcome Trust, the UK government, DBT, India, and SAMRC. We also acknowledge the University of KwaZulu-Natal for Postdoc fellowship, and CSIR-Pool officer (Pool Scientist) awarded to DB. Open access publication of this article has been made possible through support from the Victor Daitz Information Gateway, an initiative of the Victor Daitz Foundation and the University of KwaZulu-Natal.
Publisher Copyright:
© 2017 Bhattacharya, Danaviah, Muema, Akilimali, Moodley, Ndung'u and Das.
Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2017/9/11
Y1 - 2017/9/11
N2 - Mycobacterium tuberculosis (M.tb) and HIV are individually responsible for the most deaths worldwide among all infectious agents, and coinfection with M.tb and HIV is a significant public health challenge in the developing world. Although the lung is the primary target organ for tuberculosis (TB), M.tb can also cause extrapulmonary tuberculosis (EPTB) such as in the bones and joints. Treatment of EPTB is much more challenging than treatment of pulmonary TB. The hallmark of the host immune response against TB is the formation of organized structures called granulomas that are infiltrated with immune cells and are rich in cytokines and chemokines. Inside granulomas, the host confines the M.tb bacteria to a particular region of the organ and avoids dispersion. In this study, we analyzed immune cells in bone granulomas of patients with EPTB that are also coinfected with HIV. We found that HIV-infected TB patients have dispersed bone granulomas, with reduced T cell numbers and a concomitant increase in plasma cells. Additionally, HIV-infected patients exhibited dramatically increased serum levels of IgM and IgG1 antibodies, which is indicative of T-cell-independent B-cell activation and mucosal T-cell activation, respectively. Interestingly, we also observed that CD29+ stem cells are increased in HIV-TB coinfection, suggesting a link with HIV infection. Therefore, our work provides new insights into the architecture of spinal TB granulomas and the role of B-cells and humoral immunity against a highly infectious intracellular pathogen. We propose that our findings will inform biomarker identification for EPTB and possibly the development of related therapeutics and/or vaccines to protect HIV-infected patients against disseminated TB.
AB - Mycobacterium tuberculosis (M.tb) and HIV are individually responsible for the most deaths worldwide among all infectious agents, and coinfection with M.tb and HIV is a significant public health challenge in the developing world. Although the lung is the primary target organ for tuberculosis (TB), M.tb can also cause extrapulmonary tuberculosis (EPTB) such as in the bones and joints. Treatment of EPTB is much more challenging than treatment of pulmonary TB. The hallmark of the host immune response against TB is the formation of organized structures called granulomas that are infiltrated with immune cells and are rich in cytokines and chemokines. Inside granulomas, the host confines the M.tb bacteria to a particular region of the organ and avoids dispersion. In this study, we analyzed immune cells in bone granulomas of patients with EPTB that are also coinfected with HIV. We found that HIV-infected TB patients have dispersed bone granulomas, with reduced T cell numbers and a concomitant increase in plasma cells. Additionally, HIV-infected patients exhibited dramatically increased serum levels of IgM and IgG1 antibodies, which is indicative of T-cell-independent B-cell activation and mucosal T-cell activation, respectively. Interestingly, we also observed that CD29+ stem cells are increased in HIV-TB coinfection, suggesting a link with HIV infection. Therefore, our work provides new insights into the architecture of spinal TB granulomas and the role of B-cells and humoral immunity against a highly infectious intracellular pathogen. We propose that our findings will inform biomarker identification for EPTB and possibly the development of related therapeutics and/or vaccines to protect HIV-infected patients against disseminated TB.
KW - B cell
KW - Extrapulmonary tuberculosis
KW - Granuloma
KW - HIV
KW - Mesenchymal stem cells
KW - T cell
KW - Tuberculosis
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U2 - 10.3389/fimmu.2017.01120
DO - 10.3389/fimmu.2017.01120
M3 - Article
AN - SCOPUS:85029220609
VL - 8
JO - Frontiers in immunology
JF - Frontiers in immunology
SN - 1664-3224
IS - SEP
M1 - 1120
ER -