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

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• 作者：Vanessa C. Korb ^{vanessakorb@gmail.com" class="auth_mail" title="E-mail the corresponding author} ; Alisa Phulukdaree¹ ; ^{Alisa.Phulukdaree@up.ac.za" class="auth_mail" title="E-mail the corresponding author} ; Umesh G. Lalloo ^{umeshlalloo@gmail.com" class="auth_mail" title="E-mail the corresponding author} ; Anil A. Chuturgoon ; ^{chutur@ukzn.ac.za" class="auth_mail" title="E-mail the corresponding author} ; Devapregasan Moodley² ; ^{Devan_Moodley@hms.harvard.edu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Tuberculosis ; HIV ; Co-infection ; Th17 ; IL-1β ; IL-17
• 刊名：Tuberculosis
• 出版年：2016
• 出版时间：July 2016
• 年：2016
• 卷：99
• 期：Complete
• 页码：92-99
• 全文大小：908 K

文摘

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.