@article{MasicHurdayalNieuwenhuizenetal.2012,
  author    = {Masic, Anita and Hurdayal, Ramona and Nieuwenhuizen, Natalie E. and Brombacher, Frank and Moll, Heidrun},
  title     = {Dendritic Cell-Mediated Vaccination Relies on Interleukin-4 Receptor Signaling to Avoid Tissue Damage after Leishmania major Infection of BALB/c Mice},
  series = {PLoS Neglected Tropical Diseases},
  volume    = {6},
  journal   = {PLoS Neglected Tropical Diseases},
  number    = {7},
  doi       = {10.1371/journal.pntd.0001721},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-133869},
  year      = {2012},
  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-4R \(\alpha\))-deficient (CD11c\(^{cre}\)IL-4R \(\alpha^{-/lox}\) BALB/c mice were given either wt or IL-4R \(\alpha\)-deficient LmAg-loaded bone marrow-derived DC exposed or not to CpG ODN prior to inoculation of 2x10\(^5\) stationary-phase L. major promastigotes into the BALB/c footpad. The results provide evidence that IL4/IL-4R alpha-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-4R alpha-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 CD11c\(^{cre}\)IL-4R \(\alpha^{-/lox}\) mice immunized with CpG ODN-exposed LmAg-loaded IL-4R \(\alpha\)-deficient DC, indicating the influence of IL-4R \(\alpha\)-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/IL4R \(\alpha\) signaling pathway could be a key pathway to trigger when designing vaccines aimed to prevent damaging processes in tissues hosting intracellular microorganisms.},
  language  = {en}
}
@article{FirdessaGoodAmstaldenetal.2015,
  author    = {Firdessa, Rebuma and Good, Liam and Amstalden, Maria Cecilia and Chindera, Kantaraja and Kamaruzzaman, Nor Fadhilah and Schultheis, Martina and R{\"o}ger, Bianca and Hecht, Nina and Oelschlaeger, Tobias A. and Meinel, Lorenz and L{\"u}hmann, Tessa and Moll, Heidrun},
  title     = {Pathogen- and host-directed antileishmanial effects mediated by polyhexanide (PHMB)},
  series = {PLoS Neglected Tropical Diseases},
  volume    = {9},
  journal   = {PLoS Neglected Tropical Diseases},
  number    = {10},
  doi       = {10.1371/journal.pntd.0004041},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-148162},
  pages     = {e0004041},
  year      = {2015},
  abstract  = {Background Cutaneous leishmaniasis (CL) is a neglected tropical disease caused by protozoan parasites of the genus Leishmania. CL causes enormous suffering in many countries worldwide. There is no licensed vaccine against CL, and the chemotherapy options show limited efficacy and high toxicity. Localization of the parasites inside host cells is a barrier to most standard chemo- and immune-based interventions. Hence, novel drugs, which are safe, effective and readily accessible to third-world countries and/or drug delivery technologies for effective CL treatments are desperately needed. Methodology/Principal Findings Here we evaluated the antileishmanial properties and delivery potential of polyhexamethylene biguanide (PHMB; polyhexanide), a widely used antimicrobial and wound antiseptic, in the Leishmania model. PHMB showed an inherent antileishmanial activity at submicromolar concentrations. Our data revealed that PHMB kills Leishmania major (L. major) via a dual mechanism involving disruption of membrane integrity and selective chromosome condensation and damage. PHMB's DNA binding and host cell entry properties were further exploited to improve the delivery and immunomodulatory activities of unmethylated cytosine-phosphate-guanine oligodeoxynucleotides (CpG ODN). PHMB spontaneously bound CpG ODN, forming stable nanopolyplexes that enhanced uptake of CpG ODN, potentiated antimicrobial killing and reduced host cell toxicity of PHMB. Conclusions Given its low cost and long history of safe topical use, PHMB holds promise as a drug for CL therapy and delivery vehicle for nucleic acid immunomodulators.},
  language  = {en}
}