期刊
FRONTIERS IN IMMUNOLOGY
卷 10, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2019.02239
关键词
pediatric immunity; CyTOF; environment; immune development; immune profiling
类别
资金
- Canadian Institutes of Health Research
- Bill and Melinda Gates Foundation [OPP1113682]
- Howard Hughes Medical Institute
- NIH [5R01HD063142]
- NIH S10 Shared Instrument Grant [S10OD016318-01]
- Bill and Melinda Gates Foundation [OPP1113682] Funding Source: Bill and Melinda Gates Foundation
During the first 5 years of life, children are especially vulnerable to infection-related morbidity and mortality. Conversely, the Hygiene Hypothesis suggests that a lack of exposure to infectious agents early in life could explain the increasing incidence of allergies and autoimmunity in high-income countries. Understanding these phenomena, however, is hampered by a lack of comprehensive, direct immune monitoring in children with differing degrees of microbial exposure. Using mass cytometry, we provide an in-depth profile of the peripheral blood mononuclear cells (PBMCs) of children in regions at the extremes of exposure: the San Francisco Bay Area, USA and an economically poor district of Dhaka, Bangladesh. Despite variability in clinical health, functional characteristics of PBMCs were similar in Bangladeshi and American children at 1 year of age. However, by 2-3 years of age, Bangladeshi children's immune cells often demonstrated altered activation and cytokine production profiles upon stimulation with PMA-ionomycin, with an overall immune trajectory more in line with American adults. Conversely, immune responses in children from the US remained steady. Using principal component analysis, donor location, ethnic background, and cytomegalovirus infection status were found to account for some of the variation identified among samples. Within Bangladeshi 1-year-olds, stunting (as measured by height-for-age z-scores) was found to be associated with IL-8 and TGF beta expression in PMA-ionomycin stimulated samples. Combined, these findings provide important in-sights into the immune systems of children in high vs. low microbial exposure environments and suggest an important role for IL-8 and TGF beta in mitigating the microbial challenges faced by the Bangladeshi children.
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