Dendritic cell responses to Plasmodium falciparum in a malaria-endemic setting
Abstract Background Plasmodium falciparum causes the majority of malaria cases worldwide and children in sub-Saharan Africa are the most vulnerable group affected. Non-sterile clinical immunity that protects from symptoms develops slowly and is relatively short-lived. Moreover, current malaria vacci...
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Materialtyp: | Artikel |
Språk: | English |
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BMC
2021-01-01
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Serie: | Malaria Journal |
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Länkar: | https://doi.org/10.1186/s12936-020-03533-w |
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author | Triniti C. Turner Charles Arama Aissata Ongoiba Safiatou Doumbo Didier Doumtabé Kassoum Kayentao Jeff Skinner Shanping Li Boubacar Traore Peter D. Crompton Anton Götz |
author_facet | Triniti C. Turner Charles Arama Aissata Ongoiba Safiatou Doumbo Didier Doumtabé Kassoum Kayentao Jeff Skinner Shanping Li Boubacar Traore Peter D. Crompton Anton Götz |
author_sort | Triniti C. Turner |
collection | DOAJ |
description | Abstract Background Plasmodium falciparum causes the majority of malaria cases worldwide and children in sub-Saharan Africa are the most vulnerable group affected. Non-sterile clinical immunity that protects from symptoms develops slowly and is relatively short-lived. Moreover, current malaria vaccine candidates fail to induce durable high-level protection in endemic settings, possibly due to the immunomodulatory effects of the malaria parasite itself. Because dendritic cells play a crucial role in initiating immune responses, the aim of this study was to better understand the impact of cumulative malaria exposure as well as concurrent P. falciparum infection on dendritic cell phenotype and function. Methods In this cross-sectional study, the phenotype and function of dendritic cells freshly isolated from peripheral blood samples of Malian adults with a lifelong history of malaria exposure who were either uninfected (n = 27) or asymptomatically infected with P. falciparum (n = 8) was assessed. Additionally, plasma cytokine and chemokine levels were measured in these adults and in Malian children (n = 19) with acute symptomatic malaria. Results With the exception of lower plasmacytoid dendritic cell frequencies in asymptomatically infected Malian adults, peripheral blood dendritic cell subset frequencies and HLA-DR surface expression did not differ by infection status. Peripheral blood myeloid dendritic cells of uninfected Malian adults responded to in vitro stimulation with P. falciparum blood-stage parasites by up-regulating the costimulatory molecules HLA-DR, CD80, CD86 and CD40 and secreting IL-10, CXCL9 and CXCL10. In contrast, myeloid dendritic cells of asymptomatically infected Malian adults exhibited no significant responses above the uninfected red blood cell control. IL-10 and CXCL9 plasma levels were elevated in both asymptomatic adults and children with acute malaria. Conclusions The findings of this study indicate that myeloid dendritic cells of uninfected adults with a lifelong history of malaria exposure are able to up-regulate co-stimulatory molecules and produce cytokines. Whether mDCs of malaria-exposed individuals are efficient antigen-presenting cells capable of mounting an appropriate immune response remains to be determined. The data also highlights IL-10 and CXCL9 as important factors in both asymptomatic and acute malaria and add to the understanding of asymptomatic P. falciparum infections in malaria-endemic areas. |
first_indexed | 2024-12-21T13:26:18Z |
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id | doaj.art-f4c72f0bae1242f1a9377a1569d3d7d4 |
institution | Directory Open Access Journal |
issn | 1475-2875 |
language | English |
last_indexed | 2024-12-21T13:26:18Z |
publishDate | 2021-01-01 |
publisher | BMC |
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series | Malaria Journal |
spelling | doaj.art-f4c72f0bae1242f1a9377a1569d3d7d42022-12-21T19:02:26ZengBMCMalaria Journal1475-28752021-01-0120111310.1186/s12936-020-03533-wDendritic cell responses to Plasmodium falciparum in a malaria-endemic settingTriniti C. Turner0Charles Arama1Aissata Ongoiba2Safiatou Doumbo3Didier Doumtabé4Kassoum Kayentao5Jeff Skinner6Shanping Li7Boubacar Traore8Peter D. Crompton9Anton Götz10Malaria Infection Biology and Immunity Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of HealthMalaria Research and Training Centre, Department of Epidemiology of Parasitic Diseases, International Center of Excellence in Research, University of Sciences, Technique, and Technology of BamakoMalaria Research and Training Centre, Department of Epidemiology of Parasitic Diseases, International Center of Excellence in Research, University of Sciences, Technique, and Technology of BamakoMalaria Research and Training Centre, Department of Epidemiology of Parasitic Diseases, International Center of Excellence in Research, University of Sciences, Technique, and Technology of BamakoMalaria Research and Training Centre, Department of Epidemiology of Parasitic Diseases, International Center of Excellence in Research, University of Sciences, Technique, and Technology of BamakoMalaria Research and Training Centre, Department of Epidemiology of Parasitic Diseases, International Center of Excellence in Research, University of Sciences, Technique, and Technology of BamakoMalaria Infection Biology and Immunity Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of HealthMalaria Infection Biology and Immunity Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of HealthMalaria Research and Training Centre, Department of Epidemiology of Parasitic Diseases, International Center of Excellence in Research, University of Sciences, Technique, and Technology of BamakoMalaria Infection Biology and Immunity Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of HealthMalaria Infection Biology and Immunity Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of HealthAbstract Background Plasmodium falciparum causes the majority of malaria cases worldwide and children in sub-Saharan Africa are the most vulnerable group affected. Non-sterile clinical immunity that protects from symptoms develops slowly and is relatively short-lived. Moreover, current malaria vaccine candidates fail to induce durable high-level protection in endemic settings, possibly due to the immunomodulatory effects of the malaria parasite itself. Because dendritic cells play a crucial role in initiating immune responses, the aim of this study was to better understand the impact of cumulative malaria exposure as well as concurrent P. falciparum infection on dendritic cell phenotype and function. Methods In this cross-sectional study, the phenotype and function of dendritic cells freshly isolated from peripheral blood samples of Malian adults with a lifelong history of malaria exposure who were either uninfected (n = 27) or asymptomatically infected with P. falciparum (n = 8) was assessed. Additionally, plasma cytokine and chemokine levels were measured in these adults and in Malian children (n = 19) with acute symptomatic malaria. Results With the exception of lower plasmacytoid dendritic cell frequencies in asymptomatically infected Malian adults, peripheral blood dendritic cell subset frequencies and HLA-DR surface expression did not differ by infection status. Peripheral blood myeloid dendritic cells of uninfected Malian adults responded to in vitro stimulation with P. falciparum blood-stage parasites by up-regulating the costimulatory molecules HLA-DR, CD80, CD86 and CD40 and secreting IL-10, CXCL9 and CXCL10. In contrast, myeloid dendritic cells of asymptomatically infected Malian adults exhibited no significant responses above the uninfected red blood cell control. IL-10 and CXCL9 plasma levels were elevated in both asymptomatic adults and children with acute malaria. Conclusions The findings of this study indicate that myeloid dendritic cells of uninfected adults with a lifelong history of malaria exposure are able to up-regulate co-stimulatory molecules and produce cytokines. Whether mDCs of malaria-exposed individuals are efficient antigen-presenting cells capable of mounting an appropriate immune response remains to be determined. The data also highlights IL-10 and CXCL9 as important factors in both asymptomatic and acute malaria and add to the understanding of asymptomatic P. falciparum infections in malaria-endemic areas.https://doi.org/10.1186/s12936-020-03533-wDendritic cellsMalariaPlasmodium falciparumCytokinesChemokinesCostimulatory molecules |
spellingShingle | Triniti C. Turner Charles Arama Aissata Ongoiba Safiatou Doumbo Didier Doumtabé Kassoum Kayentao Jeff Skinner Shanping Li Boubacar Traore Peter D. Crompton Anton Götz Dendritic cell responses to Plasmodium falciparum in a malaria-endemic setting Malaria Journal Dendritic cells Malaria Plasmodium falciparum Cytokines Chemokines Costimulatory molecules |
title | Dendritic cell responses to Plasmodium falciparum in a malaria-endemic setting |
title_full | Dendritic cell responses to Plasmodium falciparum in a malaria-endemic setting |
title_fullStr | Dendritic cell responses to Plasmodium falciparum in a malaria-endemic setting |
title_full_unstemmed | Dendritic cell responses to Plasmodium falciparum in a malaria-endemic setting |
title_short | Dendritic cell responses to Plasmodium falciparum in a malaria-endemic setting |
title_sort | dendritic cell responses to plasmodium falciparum in a malaria endemic setting |
topic | Dendritic cells Malaria Plasmodium falciparum Cytokines Chemokines Costimulatory molecules |
url | https://doi.org/10.1186/s12936-020-03533-w |
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