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Polymer-mediated DNA vaccine delivery via bystander cells requires a proper balance between transfection efficiency and cytotoxicity.

ABSTRACT: Direct targeting of dendritic cells is an ideal goal for DNA vaccine delivery in order to stimulate both arms of the immune system. However, dendritic cells are often difficult to transfect using nonviral polyplexes. Here we show that transfecting bystander cells such as fibroblasts with PEI/DNA complexes leads to efficient cross-presentation of a model antigen by dendritic cells and subsequent activation of antigen-specific CD8(+) T cells. Maturation of dendritic cells is also stimulated after co-culture with transfected fibroblasts. Such outcomes depend on a proper balance between transfection efficiency and polyplex-induced cytotoxicity in the fibroblasts. In fact, substantial cytotoxicity is desirable and even necessary for cross-presentation and cross-priming of T cells. This study illustrates a new pathway of polymer-based DNA vaccine delivery via bystander cells without direct targeting of antigen-presenting cells and highlights the importance of exploiting polymer-induced cytotoxicity for the benefit of immune activation.

SUBMITTER: Palumbo RN

PROVIDER: S-EPMC3260377 | biostudies-literature | 2012 Jan

REPOSITORIES: biostudies-literature

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Polymer-mediated DNA vaccine delivery via bystander cells requires a proper balance between transfection efficiency and cytotoxicity.

Palumbo R Noelle RN Zhong Xiao X Wang Chun C

Journal of controlled release : official journal of the Controlled Release Society 20110901 1

Direct targeting of dendritic cells is an ideal goal for DNA vaccine delivery in order to stimulate both arms of the immune system. However, dendritic cells are often difficult to transfect using nonviral polyplexes. Here we show that transfecting bystander cells such as fibroblasts with PEI/DNA complexes leads to efficient cross-presentation of a model antigen by dendritic cells and subsequent activation of antigen-specific CD8(+) T cells. Maturation of dendritic cells is also stimulated after ...[more]

PMID: 21907252

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Project description:The first and second branchiomeric (branchial arch) muscles are craniofacial muscles that derive from branchial arch mesoderm. In mammals, this set of muscles is indispensable for jaw movement and facial expression. Defects during embryonic development that result in congenital partial absence of these muscles can have significant impact on patients' quality of life. However, the detailed molecular and cellular mechanisms that regulate branchiomeric muscle development remains poorly understood. Herein we investigated the role of retinoic acid (RA) signaling in developing branchiomeric muscles using mice as a model. We administered all-trans RA (25 mg/kg body weight) to Institute of Cancer Research (ICR) pregnant mice by gastric intubation from E8.5 to E10.5. In their embryos at E13.5, we found that muscles derived from the first branchial arch (temporalis, masseter) and second branchial arch (frontalis, orbicularis oculi) were severely affected or undetectable, while other craniofacial muscles were hypoplastic. We detected elevated cell death in the branchial arch mesoderm cells in RA-treated embryos, suggesting that excessive RA signaling reduces the survival of precursor cells of branchiomeric muscles, resulting in the development of hypoplastic craniofacial muscles. In order to uncover the signaling pathway(s) underlying this etiology, we focused on Pitx2, Tbx1, and MyoD1, which are critical for cranial muscle development. Noticeably reduced expression of all these genes was detected in the first and second branchial arch of RA-treated embryos. Moreover, elevated RA signaling resulted in a reduction in Dlx5 and Dlx6 expression in cranial neural crest cells (CNCCs), which disturbed their interactions with branchiomeric mesoderm cells. Altogether, we discovered that embryonic craniofacial muscle defects caused by excessive RA signaling were associated with the downregulation of Pitx2, Tbx1, MyoD1, and Dlx5/6, and reduced survival of cranial myogenic precursor cells.

Dataset Information

Polymer-mediated DNA vaccine delivery via bystander cells requires a proper balance between transfection efficiency and cytotoxicity.

Publications

Polymer-mediated DNA vaccine delivery via bystander cells requires a proper balance between transfection efficiency and cytotoxicity.

Similar Datasets

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