Single-Cell Analysis of Innate Cytokine Responses to Pattern Recognition Receptor Stimulation in Children across Four Continents

Smolen, K. K., Cai, B., Gelinas, L., Fortuno, E. S., Larsen, M., Speert, D. P., Chamekh, M., Cooper, Philip, Esser, M., Marchant, A. and Kollmann, T. R. (2014) 'Single-Cell Analysis of Innate Cytokine Responses to Pattern Recognition Receptor Stimulation in Children across Four Continents'. The Journal of Immunology, Vol 193, Issue 6, pp. 3003-3012.

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Abstract

Innate immunity instructs adaptive immunity, and suppression of innate immunity is associated with an increased risk for infection. We showed previously that whole-blood cellular components from a cohort of South African children secreted significantly lower levels of most cytokines following stimulation of pattern recognition receptors compared with whole blood from cohorts of Ecuadorian, Belgian, or Canadian children. To begin dissecting the responsible molecular mechanisms, we set out to identify the relevant cellular source of these differences. Across the four cohorts represented in our study, we identified significant variation in the cellular composition of whole blood; however, a significant reduction in the intracellular cytokine production on the single-cell level was only detected in South African children’s monocytes, conventional dendritic cells, and plasmacytoid dendritic cells. We also uncovered a marked reduction in polyfunctionality for each of these cellular compartments in South African children compared with children from the other continents. Together, our data identify differences in cell composition, as well as profoundly lower functional responses of innate cells, in our cohort of South African children. A possible link between altered innate immunity and increased risk for infection or lower response to vaccines in South African infants needs to be explored.

Item Type:	Article
Subjects:	QU Biochemistry > Cells and Genetics > QU 375 Cell physiology QW Microbiology and Immunology > Immunity by Type > QW 541 Natural immunity. Immunogenetics QW Microbiology and Immunology > Immunity by Type > QW 568 Cellular immunity. Immunologic cytotoxicity. Immunocompetence. Immunologic factors (General) WH Hemic and Lymphatic Systems > Hematologic Diseases. Immunologic Factors. Blood Banks > WH 450 Whole blood. Blood derivatives. Plasma substitutes. Blood expanders
Faculty: Department:	Biological Sciences > Department of Tropical Disease Biology
Digital Object Identifer (DOI):	https://doi.org/10.4049/jimmunol.1400895
Depositing User:	Lynn Roberts-Maloney
Date Deposited:	05 Jan 2015 11:50
Last Modified:	06 Feb 2018 13:08
URI:	https://archive.lstmed.ac.uk/id/eprint/4703

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