Abstract TMP112: Stroke-associated Pneumonia Impairs Pulmonary Host Defense While Infection Impairs Stroke Recovery

Abstract

Introduction: Stroke-associated pneumonia (SAP) is a common clinical complication implicated in increased morbidity and mortality after stroke. Dysphagia and stroke-induced immunodepression may contribute to SAP. However, a better understanding of the processes underlying the infection-induced immune response in the recovering brain remains to be unveiled. Methods: Stroke was modeled in mice by tMCAO (1h) followed by reperfusion; at day 3 mice received an oropharyngeal Klebsiella inoculation. To examine how lung infection affects the brain immune response, we compared tMCAo+infection vs tMCAo+vehicle. Functional outcomes and brain leukocyte cytokine expression were analyzed. To investigate how stroke affects the host response to pulmonary infection we compared Sham+infection vs tMCAo+ infection. Bacterial burden in the lung and spleen, tissue injury and immune cell profile in the lungs were evaluated at day 2 post-infection. Results/Conclusions: We detected similar brain leukocyte numbers between the tMCAo infected vs vehicle groups. However, in the tMCAo infected group, cytotoxic T-cells (CD8+) produced less IL-6 and IFNγ and granulocytes/neutrophils produced less INFγ. tMCAo infected animals also exhibited a worse functional recovery (Fig 1a). Klebsiella CFUs were increased in spleen in mice with stroke compared to sham, while lung (BAL) white blood cells counts were reduced in the stroke group, with altered cellular composition (Fig 1b).Our investigation has revealed that lung infection attenuates cytokine production in the brain after stroke. That could have a dual effect, positive for brain injury but detrimental for fighting infection. Stroke affects the response to lung infection by reducing lung leukocyte counts and increasing bacterial dissemination. Advancing our understanding of the mechanisms driving altered immune responses in SAP important for identifying potential treatment targets.