title: TB/HIV pleurisy reduces Th17 lymphocyte proportion independent of the cytokine microenvironment.
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.
authors.affiliation: Discipline of Medical Biochemistry and Chemical Pathology, University of KwaZulu-Natal, Howard College Campus, King George V Avenue, Durban 4041, South Africa. Electronic address: vanessakorb@gmail.com.
authors.forename: Vanessa C
authors.initials: VC
authors.lastname: Korb
authors.affiliation: Discipline of Medical Biochemistry and Chemical Pathology, University of KwaZulu-Natal, Howard College Campus, King George V Avenue, Durban 4041, South Africa. Electronic address: Alisa.Phulukdaree@up.ac.za.
authors.forename: Alisa
authors.initials: A
authors.lastname: Phulukdaree
authors.affiliation: Discipline of Medical Biochemistry and Chemical Pathology, University of KwaZulu-Natal, Howard College Campus, King George V Avenue, Durban 4041, South Africa. Electronic address: umeshlalloo@gmail.com.
authors.forename: Umesh G
authors.initials: UG
authors.lastname: Lalloo
authors.affiliation: Discipline of Medical Biochemistry and Chemical Pathology, University of KwaZulu-Natal, Howard College Campus, King George V Avenue, Durban 4041, South Africa. Electronic address: chutur@ukzn.ac.za.
authors.forename: Anil A
authors.initials: AA
authors.lastname: Chuturgoon
authors.affiliation: Discipline of Medical Biochemistry and Chemical Pathology, University of KwaZulu-Natal, Howard College Campus, King George V Avenue, Durban 4041, South Africa. Electronic address: Devan_Moodley@hms.harvard.edu.
authors.forename: Devapregasan
authors.initials: D
authors.lastname: Moodley
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018791:CD4 Lymphocyte Count; D016022:Case-Control Studies; D002478:Cells, Cultured; D060833:Cellular Microenvironment; D060085:Coinfection; D016207:Cytokines / Q000235:genetics / Q000276:immunology*; D005260:Female; D005786:Gene Expression Regulation; D015658:HIV Infections / Q000235:genetics / Q000276:immunology* / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D010996:Pleural Effusion / Q000276:immunology / Q000382:microbiology / Q000821:virology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology* / Q000382:microbiology / Q000821:virology; D014396:Tuberculosis, Pleural / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D014397:Tuberculosis, Pulmonary / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D055815:Young Adult
chemical_list: D016207:Cytokines; D012333:RNA, Messenger
keywords: Co-infection; HIV; IL-17; IL-1β; Th17; Tuberculosis