Interethnic differences in antigen-presenting cell activation and TLR responses in Malian children during Plasmodium falciparum malaria.

The Fulani ethnic group from West Africa is relatively better protected against Plasmodium falciparum malaria as compared to other sympatric ethnic groups, such as the Dogon. However, the mechanisms behind this lower susceptibility to malaria are largely unknown, particularly those concerning innate...

Full description

Bibliographic Details
Main Authors: Charles Arama, Pablo Giusti, Stéphanie Boström, Victor Dara, Boubacar Traore, Amagana Dolo, Ogobara Doumbo, Stefania Varani, Marita Troye-Blomberg
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2011-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3069068?pdf=render
_version_ 1811213486553825280
author Charles Arama
Pablo Giusti
Stéphanie Boström
Victor Dara
Boubacar Traore
Amagana Dolo
Ogobara Doumbo
Stefania Varani
Marita Troye-Blomberg
author_facet Charles Arama
Pablo Giusti
Stéphanie Boström
Victor Dara
Boubacar Traore
Amagana Dolo
Ogobara Doumbo
Stefania Varani
Marita Troye-Blomberg
author_sort Charles Arama
collection DOAJ
description The Fulani ethnic group from West Africa is relatively better protected against Plasmodium falciparum malaria as compared to other sympatric ethnic groups, such as the Dogon. However, the mechanisms behind this lower susceptibility to malaria are largely unknown, particularly those concerning innate immunity. Antigen-presenting cells (APCs), and in particular dendritic cells (DCs) are important components of the innate and adaptive immune systems. Therefore, in this study we investigated whether APCs obtained from Fulani and Dogon children exhibited differences in terms of activation status and toll-like receptor (TLR) responses during malaria infection. Lower frequency and increased activation was observed in circulating plasmacytoid DCs and BDCA-3+ myeloid DCs of infected Fulani as compared to their uninfected counterparts. Conversely, a higher frequency and reduced activation was observed in the same DC subsets obtained from peripheral blood of P. falciparum-infected Dogon children as compared to their uninfected peers. Moreover, infected individuals of both ethnic groups exhibited higher percentages of both classical and inflammatory monocytes that were less activated as compared to their non-infected counterparts. In line with APC impairment during malaria infection, TLR4, TLR7 and TLR9 responses were strongly inhibited by P. falciparum infection in Dogon children, while no such TLR inhibition was observed in the Fulani children. Strikingly, the TLR-induced IFN-γ release was completely abolished in the Dogon undergoing infection while no difference was seen within infected and non-infected Fulani. Thus, P. falciparum infection is associated with altered activation status of important APC subsets and strongly inhibited TLR responses in peripheral blood of Dogon children. In contrast, P. falciparum induces DC activation and does not affect the innate response to specific TLR ligands in Fulani children. These findings suggest that DCs and TLR signalling may be of importance for the protective immunity against malaria observed in the Fulani.
first_indexed 2024-04-12T05:47:35Z
format Article
id doaj.art-3ecabd5eddf341a6b6084af61529104c
institution Directory Open Access Journal
issn 1932-6203
language English
last_indexed 2024-04-12T05:47:35Z
publishDate 2011-01-01
publisher Public Library of Science (PLoS)
record_format Article
series PLoS ONE
spelling doaj.art-3ecabd5eddf341a6b6084af61529104c2022-12-22T03:45:25ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-0163e1831910.1371/journal.pone.0018319Interethnic differences in antigen-presenting cell activation and TLR responses in Malian children during Plasmodium falciparum malaria.Charles AramaPablo GiustiStéphanie BoströmVictor DaraBoubacar TraoreAmagana DoloOgobara DoumboStefania VaraniMarita Troye-BlombergThe Fulani ethnic group from West Africa is relatively better protected against Plasmodium falciparum malaria as compared to other sympatric ethnic groups, such as the Dogon. However, the mechanisms behind this lower susceptibility to malaria are largely unknown, particularly those concerning innate immunity. Antigen-presenting cells (APCs), and in particular dendritic cells (DCs) are important components of the innate and adaptive immune systems. Therefore, in this study we investigated whether APCs obtained from Fulani and Dogon children exhibited differences in terms of activation status and toll-like receptor (TLR) responses during malaria infection. Lower frequency and increased activation was observed in circulating plasmacytoid DCs and BDCA-3+ myeloid DCs of infected Fulani as compared to their uninfected counterparts. Conversely, a higher frequency and reduced activation was observed in the same DC subsets obtained from peripheral blood of P. falciparum-infected Dogon children as compared to their uninfected peers. Moreover, infected individuals of both ethnic groups exhibited higher percentages of both classical and inflammatory monocytes that were less activated as compared to their non-infected counterparts. In line with APC impairment during malaria infection, TLR4, TLR7 and TLR9 responses were strongly inhibited by P. falciparum infection in Dogon children, while no such TLR inhibition was observed in the Fulani children. Strikingly, the TLR-induced IFN-γ release was completely abolished in the Dogon undergoing infection while no difference was seen within infected and non-infected Fulani. Thus, P. falciparum infection is associated with altered activation status of important APC subsets and strongly inhibited TLR responses in peripheral blood of Dogon children. In contrast, P. falciparum induces DC activation and does not affect the innate response to specific TLR ligands in Fulani children. These findings suggest that DCs and TLR signalling may be of importance for the protective immunity against malaria observed in the Fulani.http://europepmc.org/articles/PMC3069068?pdf=render
spellingShingle Charles Arama
Pablo Giusti
Stéphanie Boström
Victor Dara
Boubacar Traore
Amagana Dolo
Ogobara Doumbo
Stefania Varani
Marita Troye-Blomberg
Interethnic differences in antigen-presenting cell activation and TLR responses in Malian children during Plasmodium falciparum malaria.
PLoS ONE
title Interethnic differences in antigen-presenting cell activation and TLR responses in Malian children during Plasmodium falciparum malaria.
title_full Interethnic differences in antigen-presenting cell activation and TLR responses in Malian children during Plasmodium falciparum malaria.
title_fullStr Interethnic differences in antigen-presenting cell activation and TLR responses in Malian children during Plasmodium falciparum malaria.
title_full_unstemmed Interethnic differences in antigen-presenting cell activation and TLR responses in Malian children during Plasmodium falciparum malaria.
title_short Interethnic differences in antigen-presenting cell activation and TLR responses in Malian children during Plasmodium falciparum malaria.
title_sort interethnic differences in antigen presenting cell activation and tlr responses in malian children during plasmodium falciparum malaria
url http://europepmc.org/articles/PMC3069068?pdf=render
work_keys_str_mv AT charlesarama interethnicdifferencesinantigenpresentingcellactivationandtlrresponsesinmalianchildrenduringplasmodiumfalciparummalaria
AT pablogiusti interethnicdifferencesinantigenpresentingcellactivationandtlrresponsesinmalianchildrenduringplasmodiumfalciparummalaria
AT stephaniebostrom interethnicdifferencesinantigenpresentingcellactivationandtlrresponsesinmalianchildrenduringplasmodiumfalciparummalaria
AT victordara interethnicdifferencesinantigenpresentingcellactivationandtlrresponsesinmalianchildrenduringplasmodiumfalciparummalaria
AT boubacartraore interethnicdifferencesinantigenpresentingcellactivationandtlrresponsesinmalianchildrenduringplasmodiumfalciparummalaria
AT amaganadolo interethnicdifferencesinantigenpresentingcellactivationandtlrresponsesinmalianchildrenduringplasmodiumfalciparummalaria
AT ogobaradoumbo interethnicdifferencesinantigenpresentingcellactivationandtlrresponsesinmalianchildrenduringplasmodiumfalciparummalaria
AT stefaniavarani interethnicdifferencesinantigenpresentingcellactivationandtlrresponsesinmalianchildrenduringplasmodiumfalciparummalaria
AT maritatroyeblomberg interethnicdifferencesinantigenpresentingcellactivationandtlrresponsesinmalianchildrenduringplasmodiumfalciparummalaria