Multidrug-Resistant Pseudomonas Aeruginosa Induce Systemic Pro-Inflammatory Immune Responses in Colonized Mice

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.