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Updated: Jul 2, 2025
Methods for Detecting Cytotoxic Amyloids Following Infection of Pulmonary Endothelial Cells by Pseudomonas aeruginosa
Published on: July 12, 2018
Tau and Aβ42 in lavage fluid of pneumonia patients are associated with end-organ dysfunction: A prospective
Phoibe Renema1,2,3, Jean-Francois Pittet4, Angela P Brandon4
1Center for Lung Biology, University of South Alabama, Mobile, Alabama, United States of America.
Background:
Bacterial pneumonia and sepsis are both common causes of end-organ dysfunction, especially in immunocompromised and critically ill patients. Pre-clinical data demonstrate that bacterial pneumonia and sepsis elicit the production of cytotoxic tau and amyloids from pulmonary endothelial cells, which cause lung and brain injury in naïve animal subjects, independent of the primary infection. The contribution of infection-elicited cytotoxic tau and amyloids to end-organ dysfunction has not been examined in the clinical setting. We hypothesized that cytotoxic tau and amyloids are present in the bronchoalveolar lavage fluid of critically ill patients with bacterial pneumonia and that these tau/amyloids are associated with end-organ dysfunction.
Methods:
Bacterial culture-positive and culture-negative mechanically ventilated patients were recruited into a prospective, exploratory observational study. Levels of tau and Aβ42 in, and cytotoxicity of, the bronchoalveolar lavage fluid were measured. Cytotoxic tau and amyloid concentrations were examined in comparison with patient clinical characteristics, including measures of end-organ dysfunction.
Results:
Tau and Aβ42 were increased in culture-positive patients (n = 49) compared to culture-negative patients (n = 50), independent of the causative bacterial organism. The mean age of patients was 52.1 ± 16.72 years old in the culture-positive group and 52.78 ± 18.18 years old in the culture-negative group. Males comprised 65.3% of the culture-positive group and 56% of the culture-negative group. Caucasian culture-positive patients had increased tau, boiled tau, and Aβ42 compared to both Caucasian and minority culture-negative patients. The increase in cytotoxins was most evident in males of all ages, and their presence was associated with end-organ dysfunction.
Conclusions:
Bacterial infection promotes the generation of cytotoxic tau and Aβ42 within the lung, and these cytotoxins contribute to end-organ dysfunction among critically ill patients. This work illuminates an unappreciated mechanism of injury in critical illness.
Insights
Bacterial pneumonia and sepsis increase cytotoxic tau and amyloid levels in the lungs, contributing to organ damage in critically ill patients. This study reveals a new mechanism of critical illness injury.
Area of Science:
- Critical care medicine
- Neuroscience
- Pathology
Background:
- Bacterial pneumonia and sepsis cause organ dysfunction, particularly in vulnerable patients.
- Pre-clinical studies suggest bacterial infections trigger cytotoxic tau and amyloid release, leading to lung and brain injury.
- The clinical relevance of these infection-elicited cytotoxins in organ dysfunction remains unclear.
Purpose of the Study:
- To investigate the presence of cytotoxic tau and amyloids in bronchoalveolar lavage fluid (BALF) of critically ill patients with bacterial pneumonia.
- To determine if these cytotoxins are associated with end-organ dysfunction in this patient population.
Main Methods:
- A prospective observational study enrolled mechanically ventilated patients with and without bacterial pneumonia.
- Levels of tau, amyloid-beta 42 (Aβ42), and BALF cytotoxicity were measured.
- Cytotoxin concentrations were correlated with clinical data, including measures of end-organ dysfunction.
Main Results:
- Tau and Aβ42 levels were elevated in patients with culture-positive bacterial pneumonia compared to culture-negative controls.
- Increased cytotoxins were observed in males and were associated with end-organ dysfunction.
- Elevated tau and Aβ42 were independent of the specific bacterial organism.
Conclusions:
- Bacterial infections stimulate the production of cytotoxic tau and Aβ42 within the lungs.
- These cytotoxins play a role in the development of end-organ dysfunction in critically ill patients.
- This research highlights an underrecognized pathway contributing to critical illness-related organ injury.
