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J Immunol. 2014 Sep 15;193(6):3003-3012. doi: 10.4049/jimmunol.1400895. Epub 2014 Aug 18.

Single-cell analysis of innate cytokine responses to pattern recognition receptor stimulation in children across four continents.

Author information

1
Department of Experimental Medicine, University of British Columbia, CFRI A5-147, 950 W28th Ave, Vancouver, BC, V5Z 4H4 Canada.
2
Department of Pediatrics, University of British Columbia, CFRI A5-147, 950 W28th Ave, Vancouver, BC, V5Z 4H4 Canada.
3
INSERM, U1135, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), F-75013, Paris, France.
4
Sorbonne Universités, Université Pierre et Marie Curie, Paris 06, CR7, CIMI-Paris, F-75013, Paris, France.
5
Institut d'Immunologie, Université Libre de Bruxelles, Charleroi, Rue Adrienne Bolland 8, Gosselies B-6041, Belgium.
6
Centro de Investigaciones FEPIS, Esmeraldas Quininde, Ecuador, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, L3 5QA, UK.
7
Molecular and Biochemical Parasitology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, L3 5QA, UK.
8
Centro de Investgación en Enfermedades Infecciosas, Escuela de Biología, Pontificia Universidad Católica del Ecuador, Casilla 17-22-20418, Quito, Ecuador Ecuador.
9
Immunology Unit, Division of Medical Microbiology, Department of Pathology, National Health Laboratory Services and Stellenbosch University, Private Bag X1, Matieland, 7602 South Africa.
10
Département de pédiatrie, Centre Hospitalier Universitaire Saint-Pierre, Rue Haute, 322 1000 Brussels, Belgium.
#
Contributed equally

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.

PMID:
25135829
PMCID:
PMC4157060
DOI:
10.4049/jimmunol.1400895
[Indexed for MEDLINE]
Free PMC Article

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