Differences in Innate Cytokine Responses between European and African Children

Abstract

Although differences in immunological responses between populations have been found in terms of vaccine efficacy, immune responses to infections and prevalence of chronic inflammatory diseases, the mechanisms responsible for these differences are not well understood. Therefore, innate cytokine responses mediated by various classes of pattern-recognition receptors including Toll-like receptors (TLR), C-type lectin receptors (CLRs) and nucleotide-binding oligomerisation domain-like receptors (NLRs) were compared between Dutch (European), semi-urban and rural Gabonese (African) children. Whole blood was stimulated for 24 hours and the pro-inflammatory tumor necrosis factor (TNF) and the anti-inflammatory/regulatory interleukin-10 (IL-10) cytokines in culture supernatant were measured by enzyme-linked immunosorbent assay (ELISA). Gabonese children had a lower pro-inflammatory response to poly(I:C) (TLR3 ligand), but a higher pro-inflammatory response to FSL-1 (TLR2/6 ligand), Pam3 (TLR2/1 ligand) and LPS (TLR4 ligand) compared to Dutch children. Anti-inflammatory responses to Pam3 were also higher in Gabonese children. Non-TLR ligands did not induce substantial cytokine production on their own. Interaction between various TLR and non-TLR receptors was further assessed, but no differences were found between the three populations. In conclusion, using a field applicable assay, significant differences were observed in cytokine responses between European and African children to TLR ligands, but not to non-TLR ligands.

Race and 30-Day Morbidity in Pediatric Urologic Surgery

“…46 One study tested various Toll-like receptor ligands by using identical protocols in children of European versus African descent and found different innate cytokine responses. 47 Clinically, black compared with white race has been significantly associated with infectious complications. Among hospitalized adult patients, blacks were found to have 34% higher odds of developing HAI, including CLABSI, UTI, and pneumonia, compared with whites.…”

Postnatal Innate Immune Development: From Birth to Adulthood

“…Furthermore, Smolen et al in a comparative study showed substantial differences in cytokine production among 2-year-old children from different continents, with more pronounced variations between the responses of South African subjects vs those from Ecuador, Belgium, and Canada ( 179 ). Significant differences in cytokine (TNF-α and IL-10) production upon TLR ligation have also been observed between Dutch and Gabonese school-aged children ( 180 ). Moreover, Tulic et al observed significant differences in the developmental trajectories of innate immune function between children with allergic disease and their non-allergic peers ( 181 ).…”

Immunomodulatory activity of pidotimod administered with standard antibiotic therapy in children hospitalized for community-acquired pneumonia

“…In comparison with adults, younger children have lower concentrations in their respiratory mucus of several proteins that exert antibacterial activity (e.g., defensins, lysozyme, IgA) as well as proteins that have immunomodulatory (e.g., secretoglobins, cytokines) and protective (e.g., trefoil proteins, heregulin) functions [ 4 – 8 ]. Moreover, a lower expression of toll-like receptors (TLRs) on epithelial cell membranes has been reported, and this leads to less efficient recognition of pathogens and a delayed and less effective induction of the innate immune response [ 9 , 10 ]. On the other hand, the activity of lymphocytes, macrophages, and dendritic cells is poor in the first years of life and tends to reach adult efficiency only after repeated exposure to infectious agents.…”