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.
Highlights
Geographical variations in responses to vaccines have been reported; for example, protection against pulmonary tuberculosis by the Bacillus Calmette–Guerin (BCG) vaccine varies from 0% to 80% in adults, with higher protection in populations living at higher latitudes [1], or the rotavirus vaccine which provided little protection against rotavirus diarrhea in Gambian infants but showed promising results in Europe [2]
Gabonese children differed in positivity for S. haematobium; semi-urban children were negative for schistosomiasis, whereas 57% of rural children were positive for this infection
This is the first study to systematically examine innate immune responses to several classes of PPRs in European and African children that originate from a semi-urban and a close-by rural area
Summary
Geographical variations in responses to vaccines have been reported; for example, protection against pulmonary tuberculosis by the Bacillus Calmette–Guerin (BCG) vaccine varies from 0% to 80% in adults, with higher protection in populations living at higher latitudes [1], or the rotavirus vaccine which provided little protection against rotavirus diarrhea in Gambian infants but showed promising results in Europe [2]. Pattern-recognition receptors (PRRs) enable the innate immune system to recognize pathogens through interaction with pathogenassociated molecular patterns. Activation of the innate immune system via the PRRs induces cytokine production and expression of costimulatory molecules, which in turn control the activation of the adaptive immune system [4,5]. Integration of information from multiple PRRs enables the immune system to tailor its response, for example through cytokine production, to counteract specific exogenous and endogenous dangers [5,6]. As PRRs form the starting point of the innate immune response, which shapes the adaptive immune response, the magnitude as well as the type of cytokines (e.g. pro- or anti-inflammatory) produced in response to stimulation of these receptors could have a major impact on health. Alterations in PRR responses can determine responses to vaccines or pathogens and to commensals, allergens or selfantigens [7,8,9]
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