Critical Role of B Cells in Toll-Like Receptor 7-Mediated Protection against Listeria monocytogenes Infection.

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. However, the widespread prophylactic use of TLR agonists has been compromised by the need to administer them by parenteral injection. An exception is the TLR7/8 agonist R848, which can boost gastrointestinal and systemic immunity when administered orally. This work examines the effect of R848 on host susceptibility to Listeria monocytogenes in a murine challenge model and describes the underlying mechanisms. Results show that prophylactic administration of R848 significantly reduces susceptibility to infection of BALB/c mice, an effect that lasts 1 week. Oral R848 directly stimulated B cells to produce cytokines and Ig. In the absence of B cells, R848-mediated protection was lost. These findings support the use of oral R848 to reduce the susceptibility of at-risk individuals to infection and identify the critical role of B cells in TLR7-mediated resistance to bacterial infection. This is a work of the U.S. Government and is not subject to copyright protection in the United States. Foreign copyrights may apply.