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

Authors

• N Kayraklioglu
• BH Horuluoglu
• M Elango
• DM Klinman

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. Unfortunately, most TLR agonists must be delivered by parenteral injection, limiting their widespread accessibility for prophylactic use. The TLR7/8 agonist R848 can be administered orally to improve immunity in both the GI tract and systemically. This work evaluates the ability of R848 to prevent GI and systemic infection by L. monocytogenes in a murine challenge model. Results show that oral R848 significantly improves host resistance to infection. Protection develops within one day of R848 administration, persists for a week, and is primarily mediated via the activation of B cells. R848 thus provides a readily accessible means of reducing susceptibility to infection among at-risk individuals.

Scientific Focus Area: Immunology

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