A TNPRC-led study investigates the immunological mechanisms that control the pathologies of a macaque model of human immunodeficiency virus (HIV) and Mycobacterium tuberculosis (Mtb), the bacterium that causes tuberculosis (TB), in individuals infected with both diseases. HIV and Mtb are the two most deadly infectious agents of humanity. One in three people are latently Mtb infected, but latent Mtb can transform into active TB. Co-infection with HIV, which can lead to acquired immunodeficiency syndrome (AIDS), and Mtb speeds the progression of both infections, a process likely driven by a depletion of CD4+ T cells. To study the immunological regulation of latent TB infection by HIV, Deepak Kaushal and colleagues at the TNPRC, Albert Einstein College of Medicine, LSU School of Veterinary Medicine, and Washington University School of Medicine infected macaques with Mtb and simian immunodeficiency virus, mimicking Mtb and HIV co-infection in humans. In a majority of animals, Mtb replication rapidly reactivated and progressed to active tuberculosis, and pathologies associated with simian immunodeficiency virus increased. Despite the decrease in pulmonary CD4+ T cells in all co-infected macaques, a third of the animals maintained tuberculosis latency. For this cohort, an increase in protective immune responses, primarily mediated by increased CD8+ and profoundly enhanced B cell responses, was associated with limited Mtb replication. Hence, this investigation points to a greater role of these immune functions in the maintenance of latency. These findings, recently published by the Proceedings of the National Academy of Sciences, USA, may provide insights into natural immunity to Mtb and could help guide the development of vaccines and immunotherapies for tuberculosis and AIDS. Based on our data, future TB vaccination strategies should incorporate the elicitation of CD8+ and B cell responses as objectives.
Source: Foreman TW*, Mehra S*, Lobato DN, Malek A, Alvarez X, Golden NA, Bucsan AS, Didier PJ, Doyle-Meyers LA, Russell-Lodrigue KE, Roy CJ, Blanchard JL, Kuroda MJ, Lackner AA, Chan J, Khader SA, Jacobs WR, Jr.#, Kaushal D#. CD4+ T-cell-independent mechanisms suppress reactivation of latent tuberculosis in a macaque model of HIV co-infection. Proc Natl Acad Sci USA. In press (to be published 09-05-2016).
MEDIA CONTACT: Deepak Kaushal, Tulane National Primate Research Center, Covington, LA; tel: 985-871-6254; e-mail:
FUNDING: This research was supported by NIH awards to DK (HL106790, RR026006, AI089323), SM (P30110760), SAK/DK (AI111914) and the TNPRC (OD011104, AI058609).
Read more at Eureka Alert Sept 5, 2016. D. Kaushal et al.
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