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.author Masic, Anita en_ZA
dc.contributor.author Hurdayal, Ramona en_ZA
dc.contributor.author Nieuwenhuizen, Natalie E en_ZA
dc.contributor.author Brombacher, Frank en_ZA
dc.contributor.author Moll, Heidrun en_ZA
dc.date.accessioned 2016-01-11T06:53:22Z
dc.date.available 2016-01-11T06:53:22Z
dc.date.issued 2012 en_ZA
dc.identifier.citation Masic, 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.0001721 en_ZA
dc.identifier.uri http://hdl.handle.net/11427/16271
dc.identifier.uri http://dx.doi.org/10.1371/journal.pntd.0001721
dc.description.abstract 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. en_ZA
dc.language.iso eng en_ZA
dc.publisher Public Library of Science en_ZA
dc.rights This 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.uri http://creativecommons.org/licenses/by/4.0 en_ZA
dc.source PLOS Neglected Tropical Diseases en_ZA
dc.source.uri http://journals.plos.org/plosntds en_ZA
dc.subject.other Leishmania major en_ZA
dc.subject.other Lymph nodes en_ZA
dc.subject.other Leishmaniasis en_ZA
dc.subject.other Vaccines en_ZA
dc.subject.other Parasite replication en_ZA
dc.subject.other Host-pathogen interactions en_ZA
dc.subject.other Mouse models en_ZA
dc.subject.other Parasitic diseases en_ZA
dc.title Dendritic cell-mediated vaccination relies on interleukin-4 receptor signaling to avoid tissue damage after Leishmania major infection of BALB/c mice en_ZA
dc.type Journal Article en_ZA
dc.rights.holder © 2012 Masic et al en_ZA
uct.type.publication Research en_ZA
uct.type.resource Article en_ZA
dc.publisher.institution University of Cape Town
dc.publisher.faculty Faculty of Health Sciences en_ZA
dc.publisher.department Institute of Infectious Disease and Molecular Medicine en_ZA
uct.type.filetype Text
uct.type.filetype Image


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This 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. Except where otherwise noted, this item's license is described as This 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.