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.

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.

CD8α+ mouse spleen dendritic cells do not originate from the CD8α- dendritic cell subset

Blood ◽  
2003 ◽  
Vol 102 (2) ◽  
pp. 601-604 ◽  
Author(s):  
Shalin Naik ◽  
David Vremec ◽  
Li Wu ◽  
Meredith O'Keeffe ◽  
Ken Shortman
Keyword(s):  
Dendritic Cells ◽  
Dendritic Cell ◽  
Balance Sheet ◽  
Rare Event ◽  
Cell Subset ◽  
Mouse Spleen ◽  
Dendritic Cell Subset

AbstractAlthough previous studies had indicated that the CD8α- and CD8α+ subtypes of murine dendritic cells (DCs) differ in immediate origin, a recent study found that intravenous transfer of CD8α- DCs led to CD8α+ DCs in the spleen several days later, suggesting a direct precursor-product relationship. We have repeated these experiments with a balance sheet approach. We find that though a few CD8α+ DCs can be generated in such experiments, this is a rare event and could be the result of a contaminant precursor. Most of the immediate precursors of CD8α+ DCs are cells that lack the phenotype of a recognizable DC. CD8α- DCs and CD8α+ DCs are not precursor-product related, though these sublineages may be connected further upstream.

scholarly journals Merocytic Dendritic Cells Compose a Conventional Dendritic Cell Subset with Low Metabolic Activity

2020 ◽  
Vol 205 (1) ◽  
pp. 121-132
Author(s):  
Cindy Audiger ◽  
Adrien Fois ◽  
Alyssa L. Thomas ◽  
Edith Janssen ◽  
Martin Pelletier ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Dendritic Cell ◽  
Metabolic Activity ◽  
Cell Subset ◽  
Dendritic Cell Subset

scholarly journals Role of the CD8+ Dendritic Cell Subset in Transmission of Prions

2007 ◽  
Vol 81 (9) ◽  
pp. 4877-4880 ◽  
Author(s):  
Shneh Sethi ◽  
Kristen M. Kerksiek ◽  
Thomas Brocker ◽  
Hans Kretzschmar
Keyword(s):  
Dendritic Cells ◽  
Dendritic Cell ◽  
Cell Subset ◽  
Transgenic Mouse Model ◽  
Oral Infection ◽  
Lymphoid Tissues ◽  
Dendritic Cell Subset ◽  
Prion Infection ◽  
Intraperitoneal Infection

ABSTRACT Controversial results have been observed in mouse models regarding the role of lymphoid tissues in prion pathogenesis. To investigate the role of dendritic cells (DC), we used a transgenic mouse model. In this model (CD11c-N17Rac1), a significant reduction of CD8+ CD11chi DC has been described, and the remaining CD8+ DC demonstrate a reduced capacity for the uptake of apoptotic cells. After intraperitoneal prion infection, significantly longer incubation times were observed in CD11c-N17Rac1 mice than in controls, indicating that a defect in CD8+ CD11chi DC significantly impedes neuroinvasion after intraperitoneal infection. In contrast, no distinct differences were observed between CD11c-N17Rac1 mice and controls after oral infection. This provides evidence that oral and intraperitoneal prion infections differ in lymphoreticular requirements.

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 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.

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