A Mouse Model of Post-Stroke Pneumonia Induced by Intra-Tracheal Inoculation with Streptococcus pneumoniae
Eva Mracsko1, Sabine Stegemann-Koniszewski, Shin-Young Na
1Department of Neurology, University Heidelberg, Heidelberg, Germany.
Background:
Stroke-induced immunodeficiency increases the risk of infectious complications, which adversely affects neurological outcome. Among those, pneumonia affects as many as one third of stroke patients and is the main contributor to mortality in the post-acute phase of stroke. Experimental findings on post-stroke susceptibility to spontaneous pneumonia in mice are contradictory. Here, we established a mouse model inducing standardized bacterial pneumonia and characterized the impaired pulmonary cellular and humoral immune responses after experimental stroke.
Methods:
Bacterial pneumonia was induced by intra-tracheal inoculation with Streptococcus pneumoniae at different time points after transient middle cerebral artery occlusion (MCAO). Bacterial counts in lungs and blood, histological changes, and cytokine production in the lungs were assessed. Furthermore, we investigated the effect of pneumonia on stroke outcome.
Results:
Intra-tracheal inoculation resulted in reproducible pneumonia and bacteraemia, and demonstrated post-stroke susceptibility to streptococcal pneumonia developing with a delay of at least 24 h after MCAO. Higher bacterial counts in mice infected 3 days after stroke induction correlated with reduced neutrophil and macrophage infiltration in the lungs and lower levels of pro-inflammatory cytokines in the broncho-alveolar lavage compared to sham-operated animals. Pneumonia increased mortality without affecting brain-infiltrating leukocytes.
Conclusions:
In this standardized mouse model of post-stroke pneumonia, we describe attenuated leukocyte infiltration and cytokine production in response to bacterial infection in the lungs that has a profound effect on outcome.
Insights
Stroke impairs lung immunity, increasing pneumonia risk and mortality. This study shows reduced immune cell and cytokine response in mice after stroke, worsening outcomes.
Area of Science:
- Immunology
- Neurology
- Infectious Diseases
Background:
- Stroke-induced immunodeficiency elevates infection risk, impacting neurological recovery.
- Pneumonia is a common complication, contributing significantly to stroke mortality.
- Existing mouse models for post-stroke pneumonia yield conflicting results.
Purpose of the Study:
- To establish a standardized mouse model for studying bacterial pneumonia after experimental stroke.
- To characterize the pulmonary immune response following stroke.
- To investigate the impact of pneumonia on stroke outcomes.
Main Methods:
- Transient middle cerebral artery occlusion (MCAO) was used to induce stroke in mice.
- Bacterial pneumonia was induced via intra-tracheal inoculation with Streptococcus pneumoniae at varying times post-MCAO.
- Immune responses (bacterial counts, histology, cytokine levels, leukocyte infiltration) and stroke outcomes were assessed.
Main Results:
- A reproducible model of post-stroke pneumonia was established, showing susceptibility at least 24 hours after MCAO.
- Mice infected 3 days post-stroke exhibited higher bacterial loads, reduced neutrophil and macrophage lung infiltration, and lower pro-inflammatory cytokine levels.
- Pneumonia increased mortality but did not alter brain-infiltrating leukocytes.
Conclusions:
- This standardized model reveals attenuated pulmonary immune responses to bacterial infection post-stroke.
- Impaired leukocyte infiltration and cytokine production contribute to adverse outcomes in post-stroke pneumonia.
