Dendritic cell-mediated vaccination relies on interleukin-4 receptor signaling to avoid tissue damage after Leishmania major infection of BALB/c mice

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dc.contributor.authorMasic, Anitaen_ZA
dc.contributor.authorHurdayal, Ramonaen_ZA
dc.contributor.authorNieuwenhuizen, Natalie Een_ZA
dc.contributor.authorBrombacher, Franken_ZA
dc.contributor.authorMoll, Heidrunen_ZA
dc.date.accessioned2016-01-11T06:53:22Z
dc.date.available2016-01-11T06:53:22Z
dc.date.issued2012en_ZA
dc.description.abstractPrevention of tissue damages at the site of Leishmania major inoculation can be achieved if the BALB/c mice are systemically given L. major antigen (LmAg)-loaded bone marrow-derived dendritic cells (DC) that had been exposed to CpG-containing oligodeoxynucleotides (CpG ODN). As previous studies allowed establishing that interleukin-4 (IL-4) is involved in the redirection of the immune response towards a type 1 profile, we were interested in further exploring the role of IL-4. Thus, wild-type (wt) BALB/c mice or DC-specific IL-4 receptor alpha (IL-4Rα)-deficient (CD11ccreIL-4Rα−/lox) BALB/c mice were given either wt or IL-4Rα-deficient LmAg-loaded bone marrow-derived DC exposed or not to CpG ODN prior to inoculation of 2×105 stationary-phase L. major promastigotes into the BALB/c footpad. The results provide evidence that IL4/IL-4Rα-mediated signaling in the vaccinating DC is required to prevent tissue damage at the site of L. major inoculation, as properly conditioned wt DC but not IL-4Rα-deficient DC were able to confer resistance. Furthermore, uncontrolled L. major population size expansion was observed in the footpad and the footpad draining lymph nodes of CD11ccreIL-4Rα−/lox mice immunized with CpG ODN-exposed LmAg-loaded IL-4Rα-deficient DC, indicating the influence of IL-4Rα-mediated signaling in host DC to control parasite replication. In addition, no footpad damage occurred in BALB/c mice that were systemically immunized with LmAg-loaded wt DC doubly exposed to CpG ODN and recombinant IL-4. We discuss these findings and suggest that the IL4/IL4Rα signaling pathway could be a key pathway to trigger when designing vaccines aimed to prevent damaging processes in tissues hosting intracellular microorganisms.en_ZA
dc.identifier.apacitationMasic, A., Hurdayal, R., Nieuwenhuizen, N. E., Brombacher, F., & Moll, H. (2012). Dendritic cell-mediated vaccination relies on interleukin-4 receptor signaling to avoid tissue damage after Leishmania major infection of BALB/c mice. <i>PLOS Neglected Tropical Diseases</i>, http://hdl.handle.net/11427/16271en_ZA
dc.identifier.chicagocitationMasic, Anita, Ramona Hurdayal, Natalie E Nieuwenhuizen, Frank Brombacher, and Heidrun Moll "Dendritic cell-mediated vaccination relies on interleukin-4 receptor signaling to avoid tissue damage after Leishmania major infection of BALB/c mice." <i>PLOS Neglected Tropical Diseases</i> (2012) http://hdl.handle.net/11427/16271en_ZA
dc.identifier.citationMasic, A., Hurdayal, R., Nieuwenhuizen, N. E., Brombacher, F., & Moll, H. (2012). Dendritic cell-mediated vaccination relies on interleukin-4 receptor signaling to avoid tissue damage after Leishmania major infection of BALB/c mice. PLoS Negl Trop Dis, 6(7), e1721. doi:10.1371/journal.pntd.0001721en_ZA
dc.identifier.ris TY - Journal Article AU - Masic, Anita AU - Hurdayal, Ramona AU - Nieuwenhuizen, Natalie E AU - Brombacher, Frank AU - Moll, Heidrun AB - Prevention of tissue damages at the site of Leishmania major inoculation can be achieved if the BALB/c mice are systemically given L. major antigen (LmAg)-loaded bone marrow-derived dendritic cells (DC) that had been exposed to CpG-containing oligodeoxynucleotides (CpG ODN). As previous studies allowed establishing that interleukin-4 (IL-4) is involved in the redirection of the immune response towards a type 1 profile, we were interested in further exploring the role of IL-4. Thus, wild-type (wt) BALB/c mice or DC-specific IL-4 receptor alpha (IL-4Rα)-deficient (CD11ccreIL-4Rα−/lox) BALB/c mice were given either wt or IL-4Rα-deficient LmAg-loaded bone marrow-derived DC exposed or not to CpG ODN prior to inoculation of 2×105 stationary-phase L. major promastigotes into the BALB/c footpad. The results provide evidence that IL4/IL-4Rα-mediated signaling in the vaccinating DC is required to prevent tissue damage at the site of L. major inoculation, as properly conditioned wt DC but not IL-4Rα-deficient DC were able to confer resistance. Furthermore, uncontrolled L. major population size expansion was observed in the footpad and the footpad draining lymph nodes of CD11ccreIL-4Rα−/lox mice immunized with CpG ODN-exposed LmAg-loaded IL-4Rα-deficient DC, indicating the influence of IL-4Rα-mediated signaling in host DC to control parasite replication. In addition, no footpad damage occurred in BALB/c mice that were systemically immunized with LmAg-loaded wt DC doubly exposed to CpG ODN and recombinant IL-4. We discuss these findings and suggest that the IL4/IL4Rα signaling pathway could be a key pathway to trigger when designing vaccines aimed to prevent damaging processes in tissues hosting intracellular microorganisms. DA - 2012 DB - OpenUCT DO - 10.1371/journal.pntd.0001721 DP - University of Cape Town J1 - PLOS Neglected Tropical Diseases LK - https://open.uct.ac.za PB - University of Cape Town PY - 2012 T1 - Dendritic cell-mediated vaccination relies on interleukin-4 receptor signaling to avoid tissue damage after Leishmania major infection of BALB/c mice TI - Dendritic cell-mediated vaccination relies on interleukin-4 receptor signaling to avoid tissue damage after Leishmania major infection of BALB/c mice UR - http://hdl.handle.net/11427/16271 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/16271
dc.identifier.urihttp://dx.doi.org/10.1371/journal.pntd.0001721
dc.identifier.vancouvercitationMasic A, Hurdayal R, Nieuwenhuizen NE, Brombacher F, Moll H. Dendritic cell-mediated vaccination relies on interleukin-4 receptor signaling to avoid tissue damage after Leishmania major infection of BALB/c mice. PLOS Neglected Tropical Diseases. 2012; http://hdl.handle.net/11427/16271.en_ZA
dc.language.isoengen_ZA
dc.publisherPublic Library of Scienceen_ZA
dc.publisher.departmentInstitute of Infectious Disease and Molecular Medicineen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_ZA
dc.rights.holder© 2012 Masic et alen_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/4.0en_ZA
dc.sourcePLOS Neglected Tropical Diseasesen_ZA
dc.source.urihttp://journals.plos.org/plosntdsen_ZA
dc.subject.otherLeishmania majoren_ZA
dc.subject.otherLymph nodesen_ZA
dc.subject.otherLeishmaniasisen_ZA
dc.subject.otherVaccinesen_ZA
dc.subject.otherParasite replicationen_ZA
dc.subject.otherHost-pathogen interactionsen_ZA
dc.subject.otherMouse modelsen_ZA
dc.subject.otherParasitic diseasesen_ZA
dc.titleDendritic cell-mediated vaccination relies on interleukin-4 receptor signaling to avoid tissue damage after Leishmania major infection of BALB/c miceen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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