Modulation of the immune response to Mycobacterium tuberculosis during malaria/M. tuberculosis co-infection

Chukwuanukwu, Rebecca C.; Onyenekwe, Charles C.; Martinez-Pomares, Luisa; Flynn, Robin J.; Singh, Sonali; Amilo, Grace I.; Agbakoba, Nneka R.; Okoye, Jude O.

Abstract

Tuberculosis (TB) causes significant morbidity and mortality on a global scale. The African region has 24% of the world's TB cases. TB overlaps with other infectious diseases such as malaria and HIV, which are also highly prevalent in the African region. TB is a leading cause of death among HIV-positive patients and co-infection with HIV and TB has been described as a syndemic. In view of the overlapping epidemiology of these diseases, it is important to understand the dynamics of the immune response to TB in the context of co-infection. We investigated the cytokine response to purified protein derivative (PPD) in peripheral blood mononuclear cells from TB patients co-infected with HIV or malaria and compared it to that of malaria- and HIV-free TB patients. A total of 231 subjects were recruited for this study and classified into six groups; untreated TB-positive, TB positive subjects on TB drugs, TB- and HIV-positive, TB- and malaria-positive, latent TB and apparently healthy control subjects. Our results demonstrate maintenance of interferon (IFN)-γ production in HIV and malaria co-infected TB patients in spite of lower CD4 counts in the HIV-infected cohort. Malaria co-infection caused an increase in the production of the T helper type 2 (Th2)-associated cytokine interleukin (IL)-4 and the anti-inflammatory cytokine IL-10 in PPD-stimulated cultures. These results suggest that malaria co-infection diverts immune response against M. tuberculosis towards a Th-2/anti-inflammatory response which might have important consequences for disease progression.

Citation

Chukwuanukwu, R. C., Onyenekwe, C. C., Martinez-Pomares, L., Flynn, R. J., Singh, S., Amilo, G. I., Agbakoba, N. R., & Okoye, J. O. (in press). Modulation of the immune response to Mycobacterium tuberculosis during malaria/M. tuberculosis co-infection. Clinical and Experimental Immunology, 187(2), https://doi.org/10.1111/cei.12861

• Journal Article Type: Article
• Acceptance Date: Aug 18, 2016
• Online Publication Date: Oct 21, 2016
• Deposit Date: Oct 21, 2016
• Publicly Available Date: Oct 21, 2016
• Journal: Clinical and Experimental Immunology
• Print ISSN: 0009-9104
• Electronic ISSN: 1365-2249
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 187
• Issue: 2
• DOI: https://doi.org/10.1111/cei.12861
• Keywords: co-infection, cytokines, HIV, malaria, tuberculosis
• Public URL: https://nottingham-repository.worktribe.com/output/822210
• Publisher URL: http://onlinelibrary.wiley.com/doi/10.1111/cei.12861/abstract
• Contract Date: Oct 21, 2016