title: Distinct cytokine and regulatory T cell profile at pleural sites of dual HIV/tuberculosis infection compared to that in the systemic circulation.
abstract: Pleural tuberculosis (TB) remains a common presentation of Mycobacterium tuberculosis (MTB) infection in HIV/TB dually infected subjects, and both cellular and acellular components of the pleural milieu promote HIV-1 replication; however, they remain uncharacterized. Using cytokine array of pleural fluid and real-time reverse transcription-polymerase chain reaction (RT-PCR) and immunophenotype analysis, pleural fluid mononuclear cells (PFMC) were compared to systemic counterparts [i.e. plasma and peripheral blood mononuclear cells (PBMC)]. Significant increases in pleural fluid cytokines compared to plasma were limited to interleukin (IL)-6, IL-8, interferon (IFN)-γ and transforming growth factor (TGF)-β, and did not include other T helper type 1 (Th1) (IL-2, IL-15), Th2 or Th17 cytokines. Patterns and levels of cytokines were indistinguishable between pleural fluid from HIV/TB and TB patients. Forkhead box P3 (FoxP3) mRNA in PFMC was increased significantly and correlated highly with levels of IL-6 and IL-8, less with TGF-β, and not with IFN-γ. Among CD4 T cells, FoxP3-reactive CD25(hi) were increased in HIV/TB dually infected subjects compared to their PBMC, and up to 15% of FoxP3(+) CD25(hi) CD4 T cells were positive for IL-8 by intracellular staining. These data implicate a dominant effect of MTB infection (compared to HIV-1) at pleural sites of dual HIV/TB infection on the local infectious milieu, that include IL-6, IL-8, IFN-γ and TGF-β and regulatory T cells (T(reg) ). A correlation in expansion of T(reg) with proinflammatory cytokines (IL-6 and IL-8) in pleural fluid was shown. T(reg) themselves may promote the inflammatory cytokine milieu through IL-8.
authors.affiliation: Division of Infectious Diseases, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106-4984, USA. zxt2@po.cwru.edu
authors.forename: Z
authors.initials: Z
authors.lastname: Toossi
authors.forename: C S
authors.initials: CS
authors.lastname: Hirsch
authors.forename: M
authors.initials: M
authors.lastname: Wu
authors.forename: H
authors.initials: H
authors.lastname: Mayanja-Kizza
authors.forename: J
authors.initials: J
authors.lastname: Baseke
authors.forename: B
authors.initials: B
authors.lastname: Thiel
mesh_terms: D000328:Adult; D016207:Cytokines / Q000097:blood / Q000378:metabolism*; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics; D015685:Fusion Proteins, gag-pol / Q000235:genetics; D015870:Gene Expression / Q000235:genetics; D015658:HIV Infections / Q000097:blood / Q000150:complications* / Q000276:immunology* / Q000378:metabolism; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D007371:Interferon-gamma / Q000097:blood / Q000378:metabolism; D015850:Interleukin-6 / Q000097:blood / Q000378:metabolism; D016209:Interleukin-8 / Q000097:blood / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010949:Plasma / Q000821:virology; D035422:Pleural Cavity / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000821:virology; D010996:Pleural Effusion / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000821:virology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014396:Tuberculosis, Pleural / Q000097:blood / Q000150:complications* / Q000276:immunology* / Q000378:metabolism; D019562:Viral Load; D055815:Young Adult
chemical_list: D016207:Cytokines; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D015685:Fusion Proteins, gag-pol; C508600:IL6 protein, human; D015850:Interleukin-6; D016209:Interleukin-8; D016212:Transforming Growth Factor beta; D007371:Interferon-gamma