@article{Hurdayal2020,
abstract = {Leishmaniasis is a vector-borne disease caused by Leishmania parasites. Macrophages are considered the primary parasite host cell, but dendritic cells (DCs) play a critical role in initiating adaptive immunity and controlling Leishmania infection. Accordingly, our previous study in CD11ccreIL-4R$\alpha$−/lox mice, which have impaired IL-4 receptor alpha (IL-4R$\alpha$) expression on CD11c+ cells including DCs, confirmed a protective role for IL-4/IL-13-responsive DCs in replication and dissemination of parasites during cutaneous leishmaniasis. However, it was unclear which DC subset/s was executing this function. To investigate this, we infected CD11ccreIL-4R$\alpha$−/lox and control mice with L. major GFP+ parasites and identified subsets of infected DCs by flow cytometry. Three days after infection, CD11b+ DCs and CD103+ DCs were the main infected DC subsets in the footpad and draining lymph node, respectively and by 4 weeks post-infection, Ly6C+ and Ly6C− CD11b+ DCs were the main infected DC populations in both the lymph nodes and footpads. Interestingly, Ly6C+CD11b+ inflammatory monocyte-derived DCs but not Ly6C−CD11b+ DCs hosted parasites in the spleen. Importantly, intracellular parasitism was significantly higher in IL-4R$\alpha$-deficient DCs. In terms of DC effector function, we found no change in the expression of pattern-recognition receptors (TLR4 and TLR9) nor in expression of the co-stimulatory marker, CD80, but MHCII expression was lower in CD11ccreIL-4R$\alpha$−/lox mice at later time-points compared to the controls. Interestingly, in CD11ccreIL-4R$\alpha$−/lox mice, which have reduced Th1 responses, CD11b+ DCs had impaired iNOS production, suggesting that DC IL-4R$\alpha$ expression and NO production is important for controlling parasite numbers and preventing dissemination. Expression of the alternative activation marker arginase was unchanged in CD11b+ DCs in CD11creIL-4R$\alpha$−/lox mice compared to littermate controls, but RELM-$\alpha$ was upregulated, suggesting IL-4R$\alpha$-independent alternative activation. In summary, L. major parasites may use Ly6C+CD11b+ inflammatory DCs derived from monocytes recruited to infection as “Trojan horses” to migrate to secondary lymphoid organs and peripheral sites, and DC IL-4R$\alpha$ expression is important for controlling infection.},
author = {Hurdayal, R. and Nieuwenhuizen, N.E. and Khutlang, R. and Brombacher, F.},
doi = {10.3389/fcimb.2019.00479},
journal = {Frontiers in Cellular and Infection Microbiology},
title = {{Inflammatory Dendritic Cells, Regulated by IL-4 Receptor Alpha Signaling, Control Replication, and Dissemination of Leishmania major in Mice}},
volume = {9},
year = {2020}
}

{"_id":"ivgPSmvttJk9586ZH","bibbaseid":"hurdayal-nieuwenhuizen-khutlang-brombacher-inflammatorydendriticcellsregulatedbyil4receptoralphasignalingcontrolreplicationanddisseminationofleishmaniamajorinmice-2020","author_short":["Hurdayal, R.","Nieuwenhuizen, N.","Khutlang, R.","Brombacher, F."],"bibdata":{"bibtype":"article","type":"article","abstract":"Leishmaniasis is a vector-borne disease caused by Leishmania parasites. Macrophages are considered the primary parasite host cell, but dendritic cells (DCs) play a critical role in initiating adaptive immunity and controlling Leishmania infection. Accordingly, our previous study in CD11ccreIL-4R$α$−/lox mice, which have impaired IL-4 receptor alpha (IL-4R$α$) expression on CD11c+ cells including DCs, confirmed a protective role for IL-4/IL-13-responsive DCs in replication and dissemination of parasites during cutaneous leishmaniasis. However, it was unclear which DC subset/s was executing this function. To investigate this, we infected CD11ccreIL-4R$α$−/lox and control mice with L. major GFP+ parasites and identified subsets of infected DCs by flow cytometry. Three days after infection, CD11b+ DCs and CD103+ DCs were the main infected DC subsets in the footpad and draining lymph node, respectively and by 4 weeks post-infection, Ly6C+ and Ly6C− CD11b+ DCs were the main infected DC populations in both the lymph nodes and footpads. Interestingly, Ly6C+CD11b+ inflammatory monocyte-derived DCs but not Ly6C−CD11b+ DCs hosted parasites in the spleen. Importantly, intracellular parasitism was significantly higher in IL-4R$α$-deficient DCs. In terms of DC effector function, we found no change in the expression of pattern-recognition receptors (TLR4 and TLR9) nor in expression of the co-stimulatory marker, CD80, but MHCII expression was lower in CD11ccreIL-4R$α$−/lox mice at later time-points compared to the controls. Interestingly, in CD11ccreIL-4R$α$−/lox mice, which have reduced Th1 responses, CD11b+ DCs had impaired iNOS production, suggesting that DC IL-4R$α$ expression and NO production is important for controlling parasite numbers and preventing dissemination. Expression of the alternative activation marker arginase was unchanged in CD11b+ DCs in CD11creIL-4R$α$−/lox mice compared to littermate controls, but RELM-$α$ was upregulated, suggesting IL-4R$α$-independent alternative activation. In summary, L. major parasites may use Ly6C+CD11b+ inflammatory DCs derived from monocytes recruited to infection as “Trojan horses” to migrate to secondary lymphoid organs and peripheral sites, and DC IL-4R$α$ expression is important for controlling infection.","author":[{"propositions":[],"lastnames":["Hurdayal"],"firstnames":["R."],"suffixes":[]},{"propositions":[],"lastnames":["Nieuwenhuizen"],"firstnames":["N.E."],"suffixes":[]},{"propositions":[],"lastnames":["Khutlang"],"firstnames":["R."],"suffixes":[]},{"propositions":[],"lastnames":["Brombacher"],"firstnames":["F."],"suffixes":[]}],"doi":"10.3389/fcimb.2019.00479","journal":"Frontiers in Cellular and Infection Microbiology","title":"Inflammatory Dendritic Cells, Regulated by IL-4 Receptor Alpha Signaling, Control Replication, and Dissemination of Leishmania major in Mice","volume":"9","year":"2020","bibtex":"@article{Hurdayal2020,\nabstract = {Leishmaniasis is a vector-borne disease caused by Leishmania parasites. Macrophages are considered the primary parasite host cell, but dendritic cells (DCs) play a critical role in initiating adaptive immunity and controlling Leishmania infection. Accordingly, our previous study in CD11ccreIL-4R$\\alpha$−/lox mice, which have impaired IL-4 receptor alpha (IL-4R$\\alpha$) expression on CD11c+ cells including DCs, confirmed a protective role for IL-4/IL-13-responsive DCs in replication and dissemination of parasites during cutaneous leishmaniasis. However, it was unclear which DC subset/s was executing this function. To investigate this, we infected CD11ccreIL-4R$\\alpha$−/lox and control mice with L. major GFP+ parasites and identified subsets of infected DCs by flow cytometry. Three days after infection, CD11b+ DCs and CD103+ DCs were the main infected DC subsets in the footpad and draining lymph node, respectively and by 4 weeks post-infection, Ly6C+ and Ly6C− CD11b+ DCs were the main infected DC populations in both the lymph nodes and footpads. Interestingly, Ly6C+CD11b+ inflammatory monocyte-derived DCs but not Ly6C−CD11b+ DCs hosted parasites in the spleen. Importantly, intracellular parasitism was significantly higher in IL-4R$\\alpha$-deficient DCs. In terms of DC effector function, we found no change in the expression of pattern-recognition receptors (TLR4 and TLR9) nor in expression of the co-stimulatory marker, CD80, but MHCII expression was lower in CD11ccreIL-4R$\\alpha$−/lox mice at later time-points compared to the controls. Interestingly, in CD11ccreIL-4R$\\alpha$−/lox mice, which have reduced Th1 responses, CD11b+ DCs had impaired iNOS production, suggesting that DC IL-4R$\\alpha$ expression and NO production is important for controlling parasite numbers and preventing dissemination. Expression of the alternative activation marker arginase was unchanged in CD11b+ DCs in CD11creIL-4R$\\alpha$−/lox mice compared to littermate controls, but RELM-$\\alpha$ was upregulated, suggesting IL-4R$\\alpha$-independent alternative activation. In summary, L. major parasites may use Ly6C+CD11b+ inflammatory DCs derived from monocytes recruited to infection as “Trojan horses” to migrate to secondary lymphoid organs and peripheral sites, and DC IL-4R$\\alpha$ expression is important for controlling infection.},\nauthor = {Hurdayal, R. and Nieuwenhuizen, N.E. and Khutlang, R. and Brombacher, F.},\ndoi = {10.3389/fcimb.2019.00479},\njournal = {Frontiers in Cellular and Infection Microbiology},\ntitle = {{Inflammatory Dendritic Cells, Regulated by IL-4 Receptor Alpha Signaling, Control Replication, and Dissemination of Leishmania major in Mice}},\nvolume = {9},\nyear = {2020}\n}\n","author_short":["Hurdayal, R.","Nieuwenhuizen, N.","Khutlang, R.","Brombacher, F."],"key":"Hurdayal2020","id":"Hurdayal2020","bibbaseid":"hurdayal-nieuwenhuizen-khutlang-brombacher-inflammatorydendriticcellsregulatedbyil4receptoralphasignalingcontrolreplicationanddisseminationofleishmaniamajorinmice-2020","role":"author","urls":{},"metadata":{"authorlinks":{}}},"bibtype":"article","biburl":"https://drive.google.com/uc?export=download&id=1-9gwO2GBrWfUK-fFo05cgfzXdRK_w9xL","dataSources":["FdCBAxFeyKEmJd8WK","wrEvssexmuYudwQw9","9bX4N36CTXtCXNFMd","Krmt6gt9ktB2s6ARh"],"keywords":[],"search_terms":["inflammatory","dendritic","cells","regulated","receptor","alpha","signaling","control","replication","dissemination","leishmania","major","mice","hurdayal","nieuwenhuizen","khutlang","brombacher"],"title":"Inflammatory Dendritic Cells, Regulated by IL-4 Receptor Alpha Signaling, Control Replication, and Dissemination of Leishmania major in Mice","year":2020}