Modulation of Antigenic Location Converts Chronic into Acute Infection by Forcing CD8+ T Cell Recognition

SummaryPathogens that reside in the phagosomes of infected cells persist despite the presence of potent T cell responses. We addressed the mechanism of immune evasion by using a mouse model of Salmonella typhimurium (ST). Recombinants of ST were generated that translocated antigen to the cytosol or phagosomes of infected cells. We find that the kinetics of antigen presentation and CD8+ T cell priming is accelerated by cytosolic antigen delivery, although the magnitude of CD8+ T cell response is not influenced by antigenic location. More importantly, only those targets that readily display antigen on the cell surface, owing to antigenic translocation to the cytosol, are recognized and killed by CD8+ T cells. Thus, vaccination approaches developed to control phagosomal pathogens should incorporate methods for modulating antigen presentation such that infected target cells can be readily recognized by CD8+ T cells.

Graphical AbstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Intracellular location of antigen governs the duration of infection ► Forcing the recognition of infected cells by CD8 T cells controls infection ► CD8 T cells can convert a chronic infection to an acute infection ► Suppression is not the cause, but the end result, of a chronic infection