HIV Progression Perturbs the Balance of the Cell-Mediated and Anti-Inflammatory Adaptive and Innate Mycobacterial Immune Response

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Abstract

Introduction. Our objective is to understand how HIV infection increases the risk of progression from latent tuberculosis (TB) to active disease. We understand now that immunity is a balance of competing immune responses by multiple cell types. Since T-lymphocyte production of interferon-gamma (IFN-γ) in response to Mycobacterium tuberculosis (Mtb) antigens fails to differentiate disease from latent infection, we applied a comprehensive profiling methodology to define immune biomarkers that reliably predict a patient's TB risk. Methods. We established a cohort of HIV-infected adults with TB disease from Swaziland. Multiparametric flow cytometry was used to quantify the mycobacterial-specific anti-inflammatory (IL-4 and IL-10) and proinflammatory (IFN-γ) immune response. Results. From 12 HIV-infected Swaziland patients with TB disease, the CD4+, CD8+, Double Negative, and CD56+CD3- lymphocytes increase their IL-4: IFN-γ ratio as HIV disease worsens (Spearman r of -0.59; -0.59; -0.60; and -0.59, resp.; p<0.05). Similarly, HIV severity is associated with an increased IL-10: IFN-γ ratio (Spearman r of -0.76; p=0.01). Conclusion. As HIV disease progresses, both the adaptive and innate branches skew away from an inflammatory and towards anti-inflammatory phenotype.

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Dinardo, A. R., Mandalakas, A. M., Maphalala, G., Mtetwa, G., Mndzebele, T., Ustero, P., … Makedonas, G. (2016). HIV Progression Perturbs the Balance of the Cell-Mediated and Anti-Inflammatory Adaptive and Innate Mycobacterial Immune Response. Mediators of Inflammation, 2016. https://doi.org/10.1155/2016/1478340

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