dendritic cell-mediated vaccination relies on interleukin-4 receptor signaling to avoid tissue damage after leishmania major infection of balbc mice树突细胞介导疫苗接种依靠interleukin-4受体信号来避免利什曼虫后组织损伤的主要感染balbc老鼠.pdfVIP

Dendritic Cell-Mediated Vaccination Relies on Interleukin-4 Receptor Signaling to Avoid Tissue Damage after Leishmania major Infection of BALB/c Mice 1 2 2 2 1 Anita Masic , Ramona Hurdayal , Natalie E. Nieuwenhuizen , Frank Brombacher , Heidrun Moll * ¨ ¨ 1 Institute for Molecular Infection Biology, University of Wurzburg, Wurzburg, Germany, 2 Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa 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-4Ra)-deficient (CD11ccreIL-4Ra2/lox) BALB/c mice were given either wt or IL-4Ra-deficient LmAg-loaded bone marrow-derived DC exposed or not to CpG ODN prior to inoculation of 2 6105 stationary-phase L. major promastigotes into the BALB/c footpad. The results provide evidence that IL4/IL-4Ra- 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-4Ra-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