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Multidrug-Resistant Pseudomonas Aeruginosa Induce Systemic Pro-Inflammatory Immune Responses in Colonized Mice
Eliane von Klitzing1, Stefan Bereswill1, Markus M Heimesaat1
1Charité - Universitätsmedizin Berlin, Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Microbiology and Hygiene, Berlin, Germany.
Abstract:
The World Health Organization has rated multidrug-resistant (MDR) Pseudomonas aeruginosa as a critical threat to human health. In the present study, we performed a survey of intestinal colonization, and local and systemic immune responses following peroral association of secondary abiotic mice with either a clinical MDR P. aeruginosa or a commensal murine Escherichia coli isolate. Depletion of the intestinal microbiota following antibiotic treatment facilitated stable intestinal colonization of both P. aeruginosa and E. coli that were neither associated with relevant clinical nor histopathological sequelae. Either stable bacterial colonization, however, resulted in distinct innate and adaptive immune cell responses in the intestines, whereas a pronounced increase in macrophages and monocytes could be observed in the small as well as large intestines upon P. aeruginosa challenge only, which also applied to colonic T lymphocytes. In addition, TNF secretion was exclusively elevated in large intestines of P. aeruginosa-colonized mice. Strikingly, association of secondary abiotic mice with MDR P. aeruginosa, but not commensal E. coli, resulted in pronounced systemic pro-inflammatory responses, whereas anti-inflammatory responses were dampened. Hence, intestinal carriage of MDR P. aeruginosa as compared to a mere commensal Gram-negative strain in otherwise healthy individuals results in distinct local and systemic pro-inflammatory sequelae.
Insights
Multidrug-resistant Pseudomonas aeruginosa colonization in mice triggered distinct local and systemic inflammatory responses compared to commensal E. coli. This highlights the significant health threat posed by MDR pathogens.
Area of Science:
- Microbiology
- Immunology
- Gastroenterology
Background:
- Multidrug-resistant (MDR) Pseudomonas aeruginosa is a critical global health threat.
- Intestinal microbiota plays a crucial role in host immune homeostasis.
- Understanding host-pathogen interactions in the gut is vital for managing infections.
Purpose of the Study:
- To investigate intestinal colonization and immune responses to MDR P. aeruginosa versus commensal E. coli.
- To compare local and systemic immune sequelae following colonization with these distinct bacterial strains.
Main Methods:
- Secondary abiotic mice were orally inoculated with MDR P. aeruginosa or commensal E. coli.
- Intestinal colonization, clinical signs, and histopathology were assessed.
- Innate and adaptive immune cell populations and cytokine (TNF) secretion were analyzed in intestinal tissues and systemically.
Main Results:
- Stable intestinal colonization by both P. aeruginosa and E. coli occurred without significant clinical or histopathological issues.
- P. aeruginosa colonization uniquely induced increased macrophages, monocytes, and colonic T lymphocytes in the intestines.
- MDR P. aeruginosa, but not E. coli, led to elevated TNF in the large intestine and pronounced systemic pro-inflammatory responses with dampened anti-inflammatory signals.
Conclusions:
- Intestinal carriage of MDR P. aeruginosa induces distinct local and systemic pro-inflammatory immune responses.
- These responses differ significantly compared to colonization with a commensal Gram-negative bacterium.
- Findings underscore the potential for MDR P. aeruginosa to cause inflammation even in otherwise healthy individuals.