Electroporation of skeletal muscle induces danger signal release and antigen-presenting cell recruitment independently of DNA vaccine administration.
BACKGROUND
Plasmid DNA vaccination combined with electroporation (EP) provides a promising approach for the prevention of infectious diseases and for cancer immunotherapy. This technology has been described as being effective in activating humoral and cellular immune response in the host as well as in enhancing expression of the encoded antigen. Several reports showed EP has adjuvant-like properties when combined with plasmid DNA injection although the effect in the absence of DNA has not been investigated.


OBJECTIVE
The aim of this study is to clarify whether the application of EP alone to the skeletal muscle is able to recruit and trigger cells involved in antigen presentation and immune response.


METHODS
Mouse skeletal muscle treated by EP were observed and processed for clinical, histological and immunohistochemistry analysis at different time points.


RESULTS
We demonstrate that EP induces transient morphological changes in the muscle with early production of endogenous cytokines responsible for signalling danger at the local level. Moreover, it causes the recruitment of inflammatory cells independently of the DNA injection and the activation of a danger pro-inflammatory pathway, resulting in T-lymphocyte migration.


CONCLUSIONS
Our data indicate EP by itself is able to recruit and trigger cells involved in antigen presentation and immune response; hence, the idea that EP has adjuvant-like properties owing to a moderate tissue injury and generation of a pro-inflammatory context with cytokine release that enhances the immune response. We suggest EP may be of practical use in clinical protocols, contributing to the development of DNA vaccination strategies.
University Campus Bio-Medico of Rome, CIR, Laboratory of Molecular Medicine and Biotechnology, Rome, Italy.
Pieranna
P
Chiarella
Emanuela
E
Massi
Mariangela
M
De Robertis
Annarita
A
Sibilio
Paola
P
Parrella
Vito Michele
VM
Fazio
Emanuela
E
Signori
D000818:Animals; D000938:Antigen-Presenting Cells / Q000378:metabolism*; D002465:Cell Movement; D016207:Cytokines / Q000378:metabolism; D018274:Electroporation; D004797:Enzyme-Linked Immunosorbent Assay; D007107:Immune System; D007150:Immunohistochemistry / Q000379:methods; D007249:Inflammation; D051379:Mice; D008809:Mice, Inbred C3H; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism; D019444:Vaccines, DNA / Q000737:chemistry* / Q000378:metabolism
D016207:Cytokines; D019444:Vaccines, DNA