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Project 1: MicroRNA as predictor and/or prognostic markers of Immune Reconstitution Inflammatory Syndrome (IRIS) in tuberculosis and HIV co-infection (project ANRS No12358)

MicroRNAs (miRs) are a group of small non-coding single-stranded RNAs (22 nucleotides) and play the important role as regulators of gene expression, physiological process and host immune response (cf. figure). Circulating miRs and exosomal miRs have also proposed as being useful as diagnostics biomarkers for numerous diseases including infectious diseases, cancer and metabolic diseases. However, the detection of miRs in biological fluid, such as plasma or serum, is very challenging and delicate, requiring specialized molecular laboratory. Flow cytometry option for miRs detection could be a best alternative way to perform high throughput screening and useful for clinical application.

Also, we demonstrated in previous study (ANRS No12153) that the degranulation capacity of NK cell plays a role in the pathogenesis of immune reconstitution inflammatory syndrome in tuberculosis and HIV co-infection and its test could be used as a predictor of IRIS. IRIS is the main challenge of early antiretroviral therapy. This pathology is currently no laboratory test could be used to diagnose, predict and/or prognosis this pathology.

This study aims to validate blood based miRs detection by flow cytometry as laboratory tool for predict and/or prognosis the clinical outcome of tuberculosis and/or HIV infected patients. To characterized miRs expression profile in HIV and /or tuberculosis diseases and to elucidate the fundamental mechanism of IRIS.

Project 2. Immunity to tuberculosis in highly immunosuppressed HIV infected and uninfected individuals. (Project NIH/NIAID, R021)

Tuberculosis is the main co-infection and cause of death in HIV-infected individuals. Our previous results in T cell associated CAMELIA study (ANRS No12164) shown that tuberculosis immune reconstitution inflammatory syndrome displayed several activation related T cells prior to antiretroviral initiation, and developed a greater post-antiretroviral therapy expansion in effector memory CD4 T cells. Moreover, tuberculosis in highly immunodeficiency HIV infected patients cause significantly greater pre-ART level of several pro-inflammatory cytokines, greater pre-antiretroviral therapy of activated CD4+ and CD8+ T cells and lower pre-antiretroviral therapy CD4+ICOS+ and CD8+CD28+ T cells, as compared to HIV mono infected patients. Therefore, the tuberculosis in HIV patient might has a long-term detrimental effect and exacerbating the premature immunological aging caused by HIV.

This study aiming to investigate peripheral blood immune senescent and methylomic signature in tuberculosis and/or HIV infected patients by analyzing T cells associated phenotypes and methylome signature and to characterize functional capacity of Th-1 like type cell to suppress Mycobactrium tuberculosis growth ex-vivo.