title: Cytokine and chemokine expression profiles in response to Mycobacterium tuberculosis stimulation are altered in HIV-infected compared to HIV-uninfected subjects with active tuberculosis.
abstract: Mycobacterium tuberculosis (Mtb) infects nearly 2 million people annually and is the most common cause of death in HIV-infected individuals. Tuberculosis (TB) diagnostics cater to HIV-uninfected individuals in non-endemic countries, are expensive, slow, and lack sensitivity for those most affected. Patterns of soluble immune markers from Mtb-stimulated immune cells are not well defined in HIV co-infection. We assessed immune differences between HIV-infected and HIV-uninfected individuals with active TB utilizing IFNγ-based QuantiFERON®-TB Gold In-Tube (QFT) testing in Nairobi, Kenya. Excess QFT supernatants were used to measure cytokine and chemokine responses by a 17-plex bead array. Mtb/HIV co-infected participants were significantly less likely to be QFT+ (47.2% versus 84.2% in the HIV-uninfected group), and demonstrated lower expression of all cytokines except for IFNα2. Receiver operator characteristic analyses identified IL-1α as a potential marker of co-infection. Among HIV-infected individuals, CD4+ T cell count correlated weakly with the expression of several analytes. Co-expression analysis highlighted differences in immune profiles between the groups. These data suggest that there is a unique and detectable Mtb-specific immune response in co-infection. A better understanding of Mtb immunology can translate into much needed immunodiagnostics with enhanced sensitivity in HIV-infected individuals, facilitating their opportunity to obtain live-saving treatment.
authors.affiliation: National HIV Research Laboratory, Public Health Agency of Canada, JC Wilt Infectious Diseases Research Laboratory, Winnipeg, Canada. Electronic address: jillian.waruk@phac-aspc.gc.ca.
authors.forename: Jillian L M
authors.initials: JL
authors.lastname: Waruk
authors.affiliation: Department of Medical Microbiology, University of Manitoba, Winnipeg, Canada; Department of Medical Microbiology, University of Nairobi, Nairobi, Kenya.
authors.forename: Zipporah
authors.initials: Z
authors.lastname: Machuki
authors.affiliation: National HIV Research Laboratory, Public Health Agency of Canada, JC Wilt Infectious Diseases Research Laboratory, Winnipeg, Canada.
authors.forename: Christine
authors.initials: C
authors.lastname: Mesa
authors.affiliation: Department of Medical Microbiology, University of Manitoba, Winnipeg, Canada.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Juno
authors.affiliation: Department of Medical Microbiology, University of Nairobi, Nairobi, Kenya.
authors.forename: Omu
authors.initials: O
authors.lastname: Anzala
authors.affiliation: Department of Medical Microbiology, University of Manitoba, Winnipeg, Canada; National Reference Centre for Mycobacteriology, Public Health Agency of Canada, Winnipeg, Canada.
authors.forename: Meenu
authors.initials: M
authors.lastname: Sharma
authors.affiliation: National HIV Research Laboratory, Public Health Agency of Canada, JC Wilt Infectious Diseases Research Laboratory, Winnipeg, Canada; Department of Medical Microbiology, University of Manitoba, Winnipeg, Canada; Department of Medical Microbiology, University of Nairobi, Nairobi, Kenya; Department of Immunology, University of Manitoba, Winnipeg, Canada.
authors.forename: T Blake
authors.initials: TB
authors.lastname: Ball
authors.affiliation: Department of Medical Microbiology, University of Manitoba, Winnipeg, Canada; Department of Medical Microbiology, University of Nairobi, Nairobi, Kenya.
authors.forename: Julius
authors.initials: J
authors.lastname: Oyugi
authors.affiliation: National HIV Research Laboratory, Public Health Agency of Canada, JC Wilt Infectious Diseases Research Laboratory, Winnipeg, Canada; Department of Medical Microbiology, University of Manitoba, Winnipeg, Canada; National Reference Centre for Mycobacteriology, Public Health Agency of Canada, Winnipeg, Canada.
authors.forename: Sandra
authors.initials: S
authors.lastname: Kiazyk
mesh_terms: D000328:Adult; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood; D018925:Chemokines / Q000097:blood*; D060085:Coinfection; D016207:Cytokines / Q000097:blood*; D005260:Female; D015658:HIV Infections / Q000097:blood* / Q000175:diagnosis / Q000276:immunology / Q000821:virology; D054884:Host-Pathogen Interactions; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D059425:Interferon-gamma Release Tests; D007630:Kenya; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000472:pathogenicity; D011237:Predictive Value of Tests; D012372:ROC Curve; D014397:Tuberculosis, Pulmonary / Q000097:blood* / Q000175:diagnosis / Q000276:immunology / Q000382:microbiology
chemical_list: D015415:Biomarkers; D018925:Chemokines; D016207:Cytokines; C573415:IFNG protein, human; D007371:Interferon-gamma
keywords: Chemokine; Co-infection; Cytokine; HIV; Interferon gamma release assay; ROC curve analysis; Tuberculosis