TB/HIV pleurisy reduces Th17 lymphocyte proportion independent of the cytokine microenvironment

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Authors

Korb, Vanessa C.
Phulukdaree, Alisa
Lalloo, Umesh G.
Chuturgoon, Anil A.
Moodley, Devapregasan

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Elsevier

Abstract

T-helper (Th) 17 cells are a pro-inflammatory subset of CD4+ effector T-cells critical in mucosal immunity. Imbalances in Th17 cell proportion have been implicated in the pathogenesis of several diseases; however, this has not been adequately explored in tuberculosis (TB) and human immunodeficiency virus (HIV) co-infection. Since Th17 cells are predominantly mucosally associated, we assessed Th17 proportion and associated microenvironment in pleural effusions from patients co-infected with TB/HIV. Our results show that TB+HIV+ pleurisy results in significantly reduced frequency of CD4+IL-17+RORC+STAT3+ Th17 cells compared to TB−HIV−ex vivo (p = 0.0054) and was confirmed in conditioned media studies in vitro (p = 0.0001). This was not associated with alterations in Th17 polarising cytokines IL-6, IL-21 and IL-23 or changes in Th17 signature cytokines IL-17A and F. However, the mRNA expression of Th17 signalling molecules, IL-6 (p = 0.0022), IL-6R (p = 0.0247), IL-1β (p = 0.0022) and signal transducer and activator (STAT) 3 (p = 0.0022) were significantly upregulated. Notably, TB+HIV+ pleural fluid contained significantly higher concentrations of IL-1β (p = 0.0008), IL-22 (p = 0.0115), IL-31 (p = 0.0210), TNF-α (p = 0.0251) and IFN-γ (p = 0.0026) than TB−HIV− pleural fluid ex vivo. Taken together, this suggests a reduced portion of Th17 lymphocytes in TB/HIV pleurisy is independent of locally mediated cytokine polarisation.

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Keywords

Co-infection, Th17, IL-17, Tuberculosis (TB), Human immunodeficiency virus (HIV), IL-1β

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Citation

Korb, VC, Phulukdaree, A, Lalloo, UGA, Chuturgoon, AA & Moodley, D 2016, 'TB/HIV pleurisy reduces Th17 lymphocyte proportion independent of the cytokine microenvironment', Tuberculosis, vol. 99, pp. 92-99.