scholarly journals Dendritic cell responses to Plasmodium falciparum in a malaria-endemic setting

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Triniti C. Turner ◽  
Charles Arama ◽  
Aissata Ongoiba ◽  
Safiatou Doumbo ◽  
Didier Doumtabé ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Dendritic Cells ◽  
Dendritic Cell ◽  
Peripheral Blood ◽  
Dendritic Cell Subset ◽  
Myeloid Dendritic Cells ◽  
Hla Dr ◽  
Malaria Exposure ◽  
History Of ◽  
And Function

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.

scholarly journals Dendritic cell responses to Plasmodium falciparum in a malaria-endemic setting

2020 ◽  
Author(s):  
Triniti C. Turner ◽  
Charles Arama ◽  
Aissata Ongoiba ◽  
Safiatou Doumbo ◽  
Didier Doumtabé ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Dendritic Cells ◽  
Dendritic Cell ◽  
Peripheral Blood ◽  
Dendritic Cell Subset ◽  
Myeloid Dendritic Cells ◽  
Hla Dr ◽  
Malaria Exposure ◽  
History Of ◽  
And Function

Abstract Background: Plasmodium falciparum causes the majority of malaria cases world-wide, mostly affecting children in sub-Saharan Africa. 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, here we sought 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 we assessed 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). Additionally, we measured plasma cytokine and chemokine levels 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: Our findings 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 our understanding of asymptomatic P. falciparum infections in malaria-endemic areas.

scholarly journals Dendritic cell responses to Plasmodium falciparum in a malaria-endemic setting

2020 ◽  
Author(s):  
Triniti C. Turner ◽  
Charles Arama ◽  
Aissata Ongoiba ◽  
Safiatou Doumbo ◽  
Didier Doumtabé ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Dendritic Cells ◽  
Dendritic Cell ◽  
Peripheral Blood ◽  
Dendritic Cell Subset ◽  
Myeloid Dendritic Cells ◽  
Hla Dr ◽  
Malaria Exposure ◽  
History Of ◽  
And Function

Abstract Background: Plasmodium falciparum causes the majority of malaria cases world-wide, mostly affecting children in sub-Saharan Africa. 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, here we sought 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 we assessed 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). Additionally, we measured plasma cytokine and chemokine levels 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: Our findings 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 in a manner that is comparable to mDCs of malaria-naïve individuals. 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 our understanding of asymptomatic P. falciparum infections in malaria-endemic areas.

scholarly journals Dendritic cell responses to Plasmodium falciparum in a malaria-endemic setting

2020 ◽  
Author(s):  
Triniti C. Turner ◽  
Charles Arama ◽  
Aissata Ongoiba ◽  
Safiatou Doumbo ◽  
Didier Doumtabé ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Dendritic Cells ◽  
Dendritic Cell ◽  
Peripheral Blood ◽  
Dendritic Cell Subset ◽  
Myeloid Dendritic Cells ◽  
Hla Dr ◽  
Malaria Exposure ◽  
History Of ◽  
And Function

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.

scholarly journals Macrophage and dendritic cell subset composition can distinguish endotypes in adjuvant-induced asthma mouse models

2021 ◽  
Author(s):  
Müge Özkan ◽  
Yusuf Cem Eskiocak ◽  
Gerhard Wingender
Keyword(s):  
Dendritic Cells ◽  
Dendritic Cell ◽  
Mouse Models ◽  
Cell Subset ◽  
Clear Understanding ◽  
Dendritic Cell Subset ◽  
Myeloid Dendritic Cells ◽  
Differential Distribution ◽  
Eosinophilic Asthma ◽  
Effective Diagnosis

Asthma is a heterogeneous disease with neutrophilic and eosinophilic asthma as the main endotypes that are distinguished according to the cells recruited to the airways and the related pathology. Eosinophilic asthma is the treatment-responsive endotype, which is mainly associated with allergic asthma. Neutrophilic asthma is a treatment-resistant endotype, affecting 5-10% of asthmatics. Although eosinophilic asthma is well-studied, a clear understanding of the endotypes is essential to devise effective diagnosis and treatment approaches for neutrophilic asthma. To this end, we directly compared adjuvant-induced mouse models of neutrophilic (CFA/OVA) and eosinophilic (Alum/OVA) asthma side-by-side. The immune response in the inflamed lung was analyzed by multi-parametric flow cytometry and immunofluorescence. We found that eosinophilic asthma was characterized by a preferential recruitment of interstitial macrophages and myeloid dendritic cells, whereas in neutrophilic asthma plasmacytoid dendritic cells, exudate macrophages, and GL7 + activated B cells predominated. This differential distribution of macrophage and dendritic cell subsets reveals important aspects of the pathophysiology of asthma and holds the promise to be used as biomarkers to diagnose asthma endotypes.

Longitudinal Peripheral Blood Lymphocyte Subsets Correlate with Decreased Disease Activity in Juvenile Dermatomyositis

2013 ◽  
Vol 40 (7) ◽  
pp. 1200-1211 ◽  
Author(s):  
Floranne C. Ernste ◽  
Cynthia S. Crowson ◽  
Consuelo Lopez de Padilla ◽  
Molly S. Hein ◽  
Ann M. Reed
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Disease Activity ◽  
Nk Cells ◽  
Peripheral Blood ◽  
Juvenile Dermatomyositis ◽  
Plasmacytoid Dendritic Cells ◽  
Myeloid Dendritic Cells ◽  
Hla Dr ◽  
Vas Scores

Objective:To determine the clinical characteristics and subsets of peripheral blood lymphocytes (PBL), which correlate with decreased disease activity in patients with juvenile dermatomyositis (JDM).Methods.Peripheral blood mononuclear cells from 24 patients with JDM were collected at Mayo Clinic Rochester between 2007 and 2011. These were analyzed using fluorescence-activated cell sorting and flow cytometry. Clinical disease activity was determined by visual analog scales (VAS) collected in 2 consecutive visits and correlated with PBL subsets.Results.The change in CD3+CD69+ T cells correlated with the change in global VAS scores. The change in HLA-DR- CD11c+ myeloid dendritic cells also correlated with the change in extramuscular VAS scores. There were trends toward decreased levels of HLA-DR- CD11c+ cells with decreased muscle and global VAS scores, but these did not reach significance. The change in HLA-DR- CD123+ plasmacytoid dendritic cells negatively correlated with the change in muscle VAS scores. Although not statistically significant, decreased levels of CD3-CD16- CD56+ natural killer (NK) cells and HLA-DR- CD86+ myeloid dendritic cells, and increased levels of CD16+CD56- NK cells, correlated with decreased VAS scores.Conclusion.Changes in CD3+CD69+ T cells, HLA-DR- CD11c+ myeloid dendritic cells, and HLA-DR- CD123+ plasmacytoid dendritic cells are associated with improved clinical course in JDM and could be used as markers for disease activity, but findings need to be verified in a larger, independent cohort. Lack of significant differences among most of our PBL subsets suggests that lymphocyte phenotyping may be difficult to definitively correlate with disease activity in JDM.

scholarly journals The human syndrome of dendritic cell, monocyte, B and NK lymphoid deficiency

2011 ◽  
Vol 208 (2) ◽  
pp. 227-234 ◽  
Author(s):  
Venetia Bigley ◽  
Muzlifah Haniffa ◽  
Sergei Doulatov ◽  
Xiao-Nong Wang ◽  
Rachel Dickinson ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Dendritic Cells ◽  
Dendritic Cell ◽  
Peripheral Blood ◽  
Langerhans Cells ◽  
Elevated Serum ◽  
Blood Compartment ◽  
Hla Dr ◽  
Epidermal Langerhans Cells

Congenital or acquired cellular deficiencies in humans have the potential to reveal much about normal hematopoiesis and immune function. We show that a recently described syndrome of monocytopenia, B and NK lymphoid deficiency additionally includes the near absence of dendritic cells. Four subjects showed severe depletion of the peripheral blood HLA-DR+ lineage− compartment, with virtually no CD123+ or CD11c+ dendritic cells (DCs) and very few CD14+ or CD16+ monocytes. The only remaining HLA-DR+ lineage− cells were circulating CD34+ progenitor cells. Dermal CD14+ and CD1a+ DC were also absent, consistent with their dependence on blood-derived precursors. In contrast, epidermal Langerhans cells and tissue macrophages were largely preserved. Combined loss of peripheral DCs, monocytes, and B and NK lymphocytes was mirrored in the bone marrow by complete absence of multilymphoid progenitors and depletion of granulocyte-macrophage progenitors. Depletion of the HLA-DR+ peripheral blood compartment was associated with elevated serum fms-like tyrosine kinase ligand and reduced circulating CD4+CD25hiFoxP3+ T cells, supporting a role for DC in T reg cell homeostasis.

scholarly journals Cord Blood Dendritic Cell Subsets in African Newborns Exposed to Plasmodium falciparum In Utero

2006 ◽  
Vol 74 (10) ◽  
pp. 5725-5729 ◽  
Author(s):  
Lutz P. Breitling ◽  
Rolf Fendel ◽  
Benjamin Mordmueller ◽  
Ayola A. Adegnika ◽  
Peter G. Kremsner ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Dendritic Cells ◽  
Cord Blood ◽  
Interleukin 10 ◽  
In Utero ◽  
Maternal Infection ◽  
Myeloid Dendritic Cells ◽  
Hla Dr ◽  
Regulatory Type ◽  
Blood Dendritic Cell

ABSTRACT Placental Plasmodium falciparum infection affects birth outcomes and sensitizes fetal lymphocytes to parasite antigens. We assessed the influence of maternal P. falciparum infection on fetal myeloid dendritic cells (mDC) and plasmacytoid dendritic cells (pDC), analyzing the cord blood of offspring of Gabonese mothers with different infection histories. Cord blood from newborns of mothers with malarial infection at delivery had significantly more mDC than that from nonexposed newborns (P = 0.028) but mDC and pDC HLA-DR expression was unrelated to maternal infection history. Independently of these findings, cord blood mDC and pDC numbers declined significantly as a function of increasing maternal age (P = 0.029 and P = 0.033, respectively). The inducible antigen-specific interleukin-10-producing regulatory-type T-cell population that we have previously detected in cord blood of newborns with prolonged in utero exposure to P. falciparum may directly reflect the altered DC numbers in such neonates, while the maintenance of cord blood DC HLA-DR expression contrasts with that of DC from P. falciparum malaria patients.

scholarly journals Macrophage and dendritic cell subset composition can distinguish endotypes in adjuvant-induced asthma mouse models

PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0250533
Author(s):  
Müge Özkan ◽  
Yusuf Cem Eskiocak ◽  
Gerhard Wingender
Keyword(s):  
Dendritic Cells ◽  
Dendritic Cell ◽  
Mouse Models ◽  
Cell Subset ◽  
Clear Understanding ◽  
Dendritic Cell Subset ◽  
Myeloid Dendritic Cells ◽  
Differential Distribution ◽  
Eosinophilic Asthma ◽  
Effective Diagnosis

Asthma is a heterogeneous disease with neutrophilic and eosinophilic asthma as the main endotypes that are distinguished according to the cells recruited to the airways and the related pathology. Eosinophilic asthma is the treatment-responsive endotype, which is mainly associated with allergic asthma. Neutrophilic asthma is a treatment-resistant endotype, affecting 5–10% of asthmatics. Although eosinophilic asthma is well-studied, a clear understanding of the endotypes is essential to devise effective diagnosis and treatment approaches for neutrophilic asthma. To this end, we directly compared adjuvant-induced mouse models of neutrophilic (CFA/OVA) and eosinophilic (Alum/OVA) asthma side-by-side. The immune response in the inflamed lung was analyzed by multi-parametric flow cytometry and immunofluorescence. We found that eosinophilic asthma was characterized by a preferential recruitment of interstitial macrophages and myeloid dendritic cells, whereas in neutrophilic asthma plasmacytoid dendritic cells, exudate macrophages, and GL7+ activated B cells predominated. This differential distribution of macrophage and dendritic cell subsets reveals important aspects of the pathophysiology of asthma and holds the promise to be used as biomarkers to diagnose asthma endotypes.

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