RESUMO
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-1ß (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-1ß (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.
Assuntos
Microambiente Celular , Coinfecção , Citocinas/imunologia , Infecções por HIV/imunologia , Células Th17/imunologia , Tuberculose Pleural/imunologia , Tuberculose Pulmonar/imunologia , Adolescente , Adulto , Idoso , Contagem de Linfócito CD4 , Estudos de Casos e Controles , Células Cultivadas , Citocinas/genética , Feminino , Regulação da Expressão Gênica , Infecções por HIV/genética , Infecções por HIV/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Derrame Pleural/imunologia , Derrame Pleural/microbiologia , Derrame Pleural/virologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Células Th17/microbiologia , Células Th17/virologia , Tuberculose Pleural/genética , Tuberculose Pleural/microbiologia , Tuberculose Pulmonar/genética , Tuberculose Pulmonar/microbiologia , Adulto JovemRESUMO
Mycobacterium tuberculosis (MTB) is one of the most successful pathogens in human history and remains a global health challenge. MTB has evolved a plethora of strategies to evade the immune response sufficiently to survive within the macrophage in a bacterial-immunological equilibrium, yet causes sufficient immunopathology to facilitate its transmission. This review highlights MTB as the driver of disease pathogenesis and presents evidence of the mechanisms by which MTB manipulates the protective immune response into a pathological productive infection.
