Phenotypically resembling myeloid derived suppressor cells are increased in children with HIV and exposed/infected with Mycobacterium tuberculosis

被引:25
作者
Du Plessis, Nelita [1 ]
Jacobs, Ruschca [1 ]
Gutschmidt, Andrea [1 ]
Fang, Zhuo [1 ]
van Helden, Paul D. [1 ]
Lutz, Manfred B. [2 ]
Hesseling, Anneke C. [3 ]
Walzl, Gerhard [1 ]
机构
[1] Univ Stellenbosch, Fac Med & Hlth Sci, DST & NRF Ctr Excellence Biomed TB Res, Div Mol Biol & Human Genet,Dept Biomed Sci,SAMRC, Stellenbosch, South Africa
[2] Univ Wurzburg, Inst Virol & Immunobiol, Wurzburg, Germany
[3] Univ Stellenbosch, Fac Hlth Sci, Dept Paediat & Child Hlth, Desmond Tutu TB Ctr, Tygerberg, South Africa
基金
美国国家卫生研究院;
关键词
Children; Early life immunity; HIV exposure; Myeloid derived suppressor cells (MDSCs); Tuberculosis; IMMUNE-RESPONSES; CORRELATE; SUBSETS; IDENTIFICATION; EXPRESSION; MORTALITY; INFECTION; RISK;
D O I
10.1002/eji.201646658
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:107 / 118
页数:12
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