Cellular Architecture of Spinal Granulomas and the Immunological Response in Tuberculosis Patients Coinfected with HIV

Abstract

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.

Curcumin Nanoparticles Enhance Mycobacterium bovis BCG Vaccine Efficacy by Modulating Host Immune Responses

“…Pieces of lungs from mice 75 days after infection were perfused, removed, fixed in 4.5% formalin for 12 h, and transferred to 70% ethanol; paraffin blocks were then made; and 6-μm sections were cut and stained with hematoxylin and eosin according to our previous work (58).…”

Pathogenesis of Human Immunodeficiency Virus-Mycobacterium tuberculosis Co-Infection

“…Not all granulomas are similar in content; as HIV progresses, the characteristics of TB granulomas evolve [72]. Studies indicate that peripheral CD4 (pCD4) T cells play a significant role in granuloma formation.…”

Evaluation of immunoglobulin M and A level in individuals with HIV-TB co-infection in NAUTH, Nnewi

“…13 Together, HIV and Mycobacterium tuberculosis are the two leading causes of death among people living with HIV, accounting for one in four HIV-related deaths, 14,15 and continue to pose serious significant public health challenge in developing countries. 15,16 At least one-third of the people living with HIV worldwide are infected with latent Mycobacterium tuberculosis. 14 Varying prevalence of HIV-TB co-infection has been documented previous in both male and female individuals.…”