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Updated: Apr 25, 2026

Single-cell Analysis of Immunophenotype and Cytokine Production in Peripheral Whole Blood via Mass Cytometry
Published on: June 26, 2018
Single-cell analysis of innate cytokine responses to pattern recognition receptor stimulation in children across four
Kinga K Smolen1, Bing Cai2, Edgardo S Fortuno2
1Department of Experimental Medicine, University of British Columbia, CFRI A5-147, 950 W28th Ave, Vancouver, BC, V5Z 4H4 Canada.
Insights
South African children show reduced innate immune cell function, specifically lower cytokine production and polyfunctionality in monocytes and dendritic cells. This innate immune difference may increase infection risk or lower vaccine response in infants.
Area of Science:
- Immunology
- Infectious Disease Epidemiology
- Cellular Biology
Background:
- Innate immunity is crucial for adaptive immunity and infection defense.
- Previous studies indicated lower cytokine secretion in South African children's blood cells.
- Understanding cellular sources of immune differences is vital for public health.
Purpose of the Study:
- To identify the specific innate immune cells responsible for reduced cytokine production in South African children.
- To compare the cellular composition and function across diverse geographic cohorts.
- To investigate differences in immune cell polyfunctionality.
Main Methods:
- Analysis of whole-blood cellular composition across four international cohorts.
- Single-cell intracellular cytokine production assays following pattern recognition receptor stimulation.
- Comparative analysis of monocyte, conventional dendritic cell, and plasmacytoid dendritic cell function.
Main Results:
- Significant variations in blood cell composition were observed across cohorts.
- South African children exhibited reduced intracellular cytokine production in monocytes and dendritic cells.
- A marked decrease in immune cell polyfunctionality was noted in South African children.
Conclusions:
- Innate immune cells, including monocytes and dendritic cells, show profoundly lower functional responses in South African children.
- Differences in cell composition and function contribute to altered innate immunity.
- Further research is needed to explore links between altered innate immunity and infection risk or vaccine response in South African infants.
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.

