Impact Of Key Nicotinic Achr Subunits On Post-Stroke Pneumococcal Pneumonia

Pneumonia is the most frequent severe medical complication after stroke. An overactivation of the cholinergic signaling after stroke contributes to immunosuppression and the development of spontaneous pneumonia caused by Gram-negative pathogens. The alpha 7 nicotinic acetylcholine receptor (alpha 7nAChR) has already been identified as an important mediator of the anti-inflammatory pathway after stroke. However, whether the alpha 2, alpha 5 and alpha 9/10 nAChR expressed in the lung also play a role in suppression of pulmonary innate immunity after stroke is unknown. In the present study, we investigate the impact of various nAChRs on aspiration-induced pneumonia after stroke. Therefore, alpha 2, alpha 5, alpha 7 and alpha 9/10 nAChR knockout (KO) mice and wild type (WT) littermates were infected withStreptococcus pneumoniae(S. pneumoniae) three days after middle cerebral artery occlusion (MCAo). One day after infection pathogen clearance, cellularity in lung and spleen, cytokine secretion in bronchoalveolar lavage (BAL) and alveolar-capillary barrier were investigated. Here, we found that deficiency of various nAChRs does not contribute to an enhanced clearance of a Gram-positive pathogen causing post-stroke pneumonia in mice. In conclusion, these findings suggest that a single nAChR is not sufficient to mediate the impaired pulmonary defense againstS. pneumoniaeafter experimental stroke.