Why Does an I.M. Immunization Work?

The skeletal muscle has been long viewed as a site of election for immunization due to the sustained stay of the antigens in this tissue. Besides a passive function during immune priming, however, recent studies have shed light on an active role of muscle cells (fibers, satellite cells, and stromal cells) in inflammatory and immune response. In this context, the chemical nature of the antigen (into tissues and cells?) and the choice of adjuvants contribute to determine the fate of the antigen itself and the resulting immune response. In particular, this applies to modern vaccine approaches that involve the use of nucleic acid to locally synthesize the protein antigen. Based on these novel concepts, the possibility of manipulating therapeutically the mechanisms of peripheral tolerance at the level of muscle tissue will be discussed in the light of the recent literature.