Oral R848 Reduces Host Susceptibility to Enteric and Systemic L. monocytogenes Challenge

Abstract Toll-like receptors (TLR) trigger the immune system to mount a rapid innate response capable of protecting the host from a wide variety of bacterial and viral pathogens. There is interest in harnessing TLR agonists to reduce the susceptibility of at-risk populations to infection. Yet the widespread prophylactic use of TLR agonists is compromised by the need to administer most of them by parenteral injection. An exception is the TLR7/8 agonist R848 which can boost GI and systemic immunity when administered orally. This work examines the effect of R848 on host susceptibility to L. monocytogenes in a murine challenge model. Results show that prophylactic administration of R848 significantly reduced susceptibility to infection over the ensuing 1–7 days in Balb/C mice. Oral R848 led directly to B cell stimulation and accelerated the response of T cells to subsequent L. monocytogenes challenge. Oral R848 may thus be of use in reducing the susceptibility of at-risk individuals to infection.