A1 Adenosine Receptor Signaling ReducesStreptococcus pneumoniaeAdherence to Pulmonary Epithelial Cells by Targeting Expression of Platelet-Activating Factor Receptor

Abstract

SummaryExtracellular adenosine production is crucial for host resistance againstStreptococcus pneumoniae(pneumococcus) and is thought to affect antibacterial immune responses by neutrophils. However, whether extracellular adenosine alters direct host-pathogen interaction remains unexplored. An important determinant for lung infection byS. pneumoniaeis its ability to adhere to the pulmonary epithelium. Here we explored whether extracellular adenosine can directly impact bacterial adherence to lung epithelial cells. We found signaling via A1 adenosine receptor significantly reduced the ability of pneumococci to bind human pulmonary epithelial cells. A1 receptor signaling blocked bacterial binding by reducing the expression of platelet-activating factor receptor, a host protein used byS. pneumoniaeto adhere to host cells.In vivo, A1 was required for control of pneumococcal pneumonia as inhibiting it resulted in increased host susceptibility. AsS. pneumoniaeremain a leading cause of community-acquired pneumonia in the elderly, we explored the role of A1 in the age-driven susceptibility to infection. We found no difference in A1 pulmonary expression in young versus old mice. Strikingly, triggering A1 signaling boosted host resistance of old mice toS. pneumoniaepulmonary infection. This study demonstrates a novel mechanism by which extracellular adenosine modulates resistance to lung infection by targeting bacterial-host interactions.