| Title: | Differential Gene Expression in the Immunometabolic Response of Human Macrophages in tuberculosis and HIV infection. |
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| Author(s): | K Brown M O'Sullivan S O'Leary J Keane |
| Institution: | TTMI, St. James' Hospital |
| Poster: | Click to view poster |
| Category: | CF and Pulmonary Infections |
| Abstract: | Intro Tuberculosis (TB) is the world’s leading infectious disease, and TB/HIV co-infection represents a major barrier to effective disease management. Novel TB therapeutics research focuses on embellishing the host response, specifically on the alveolar macrophage’s ability to clear infection, which is altered by HIV. Much of this work is on immunometabolism. Disrupted TCA cycle flux is a hallmark of macrophage polarisation and the immunometabolic response. Aim We hypothesised that HIV infection would alter the immunometabolic response of human macrophages to Mtb infection, and that these infections would also lead to differential microRNA profiles. Methods Chronically HIV-infected U1, and their control U937, cells were infected with Mtb (H37Rv). Human MDM were infected with Mtb (H37Ra) or stimulated with HIV gp120. Cell lysates were harvested 24 hours following infection and RNA analysed by real time RT-PCR. Results HIV infection altered the expression of TCA cycle enzymes during Mtb infection. Mtb and HIV gp120 stimulation resulted in differential expression of miR-378a-3p, which targets aconitate decarboxylase (ACOD1) – the enzyme responsible for itaconate production. Discussion HIV alters the immunometabolic reponse of human macrophages in Mtb infection. Restricted itaconate synthesis following miR-378a-3p induction during HIV infection could hamper the anti-tuberculous response. Targeting this microRNA may represent an avenue for host-directed immunotherapy. |
