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

• Published in: Tuberculosis (Edinburgh, Scotland) Vol. 99; pp. 92 - 99
• Main Authors: Korb, Vanessa C, Phulukdaree, Alisa, Lalloo, Umesh G, Chuturgoon, Anil A, Moodley, Devapregasan
• Format: Journal Article
• Language: English
• Published: Scotland Elsevier Ltd 01-07-2016
• Subjects: Adolescent; Adult; Aged; Case-Control Studies; CD4 Lymphocyte Count; Cells, Cultured; Cellular Microenvironment; Co-infection; Coinfection; Cytokines - genetics; Cytokines - immunology; Female; Gene Expression Regulation; HIV; HIV Infections - genetics; HIV Infections - immunology; HIV Infections - virology; Humans; IL-17; IL-1β; Infectious Disease; Male; Middle Aged; Phenotype; Pleural Effusion - immunology; Pleural Effusion - microbiology; Pleural Effusion - virology; Pulmonary/Respiratory; RNA, Messenger - genetics; RNA, Messenger - metabolism; Th17; Th17 Cells - immunology; Th17 Cells - microbiology; Th17 Cells - virology; Tuberculosis; Tuberculosis, Pleural - genetics; Tuberculosis, Pleural - immunology; Tuberculosis, Pleural - microbiology; Tuberculosis, Pulmonary - genetics; Tuberculosis, Pulmonary - immunology; Tuberculosis, Pulmonary - microbiology; Young Adult; Tuberculosis; Co-infection; HIV; IL-1β; Th17; IL-17
• ISSN: 1472-9792; 1873-281X
• DOI: 10.1016/j.tube.2016.05.001

Summary 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.