title: Phenotypically resembling myeloid derived suppressor cells are increased in children with HIV and exposed/infected with Mycobacterium tuberculosis.
abstract: Increased disease susceptibility during early life has been linked to immune immaturity, regulatory T-cell/TH2 immune biasing and hyporesponsiveness. The contribution of myeloid derived suppressor cells (MDSCs) remains uninvestigated. Here, we assessed peripheral MDSC in HIV-infected and -uninfected children with tuberculosis (TB) disease before, during and after TB treatment, along with matched household contacts (HHCs), HIV-exposed, -infected and -uninfected children without recent TB exposure. Serum analytes and enzymes associated with MDSC accumulation/activation/function were measured by colorimetric- and fluorescence arrays. Peripheral frequencies of cells phenotypically resembling MDSCs were significantly increased in HIV-exposed uninfected (HEU) and M.tb-infected children, but peaked in children with TB disease and remained high following treatment. MDSC in HIV-infected (HI) children were similar to unexposed uninfected controls; however, HAART-mediated MDSC restoration to control levels could not be disregarded. Increased MDSC frequencies in HHC coincided with enhanced indoleamine-pyrrole-2,3-dioxygenase (IDO), whereas increased MDSC in TB cases were linked to heightened IDO and arginase-1. Increased MDSC were paralleled by reduced plasma IP-10 and thrombospondin-2 levels in HEU and significantly increased plasma IL-6 in HI HHC. Current investigations into MDSC-targeted treatment strategies, together with functional analyses of MDSCs, could endorse these cells as novel innate immune regulatory mechanism of infant HIV/TB susceptibility.
authors.affiliation: Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences/SAMRC Centre for Tuberculosis Research/DST and NRF Centre of Excellence for Biomedical TB Research, Faculty of Medicine and Health Sciences, Stellenbosch University, Stellenbosch, South Africa.
authors.forename: Nelita
authors.initials: N
authors.lastname: Du Plessis
authors.affiliation: Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences/SAMRC Centre for Tuberculosis Research/DST and NRF Centre of Excellence for Biomedical TB Research, Faculty of Medicine and Health Sciences, Stellenbosch University, Stellenbosch, South Africa.
authors.forename: Ruschca
authors.initials: R
authors.lastname: Jacobs
authors.affiliation: Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences/SAMRC Centre for Tuberculosis Research/DST and NRF Centre of Excellence for Biomedical TB Research, Faculty of Medicine and Health Sciences, Stellenbosch University, Stellenbosch, South Africa.
authors.forename: Andrea
authors.initials: A
authors.lastname: Gutschmidt
authors.affiliation: Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences/SAMRC Centre for Tuberculosis Research/DST and NRF Centre of Excellence for Biomedical TB Research, Faculty of Medicine and Health Sciences, Stellenbosch University, Stellenbosch, South Africa.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Fang
authors.affiliation: Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences/SAMRC Centre for Tuberculosis Research/DST and NRF Centre of Excellence for Biomedical TB Research, Faculty of Medicine and Health Sciences, Stellenbosch University, Stellenbosch, South Africa.
authors.forename: Paul D
authors.initials: PD
authors.lastname: van Helden
authors.affiliation: Institute of Virology and Immunobiology, University of Würzburg, Würzburg, Germany.
authors.forename: Manfred B
authors.initials: MB
authors.lastname: Lutz
authors.affiliation: Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Health Sciences, Stellenbosch University, Tygerberg, South Africa.
authors.forename: Anneke C
authors.initials: AC
authors.lastname: Hesseling
authors.affiliation: Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences/SAMRC Centre for Tuberculosis Research/DST and NRF Centre of Excellence for Biomedical TB Research, Faculty of Medicine and Health Sciences, Stellenbosch University, Stellenbosch, South Africa.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Walzl
mesh_terms: D023241:Antiretroviral Therapy, Highly Active; D001119:Arginase / Q000097:blood; D015415:Biomarkers; D002452:Cell Count; D002675:Child, Preschool; D060085:Coinfection; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D005260:Female; D015658:HIV Infections / Q000175:diagnosis / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000097:blood; D007223:Infant; D008297:Male; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D000072737:Myeloid-Derived Suppressor Cells / Q000276:immunology* / Q000378:metabolism*; D010641:Phenotype; D014376:Tuberculosis / Q000175:diagnosis / Q000188:drug therapy / Q000276:immunology* / Q000517:prevention & control
chemical_list: D015415:Biomarkers; D016207:Cytokines; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D001119:Arginase
keywords: Children; Early life immunity; HIV exposure; Myeloid derived suppressor cells (MDSCs); Tuberculosis