Acidosis exacerbates in vivo IL-1-dependent inflammatory responses and neutrophil recruitment during pulmonaryPseudomonas aeruginosainfection

Acidic microenvironments commonly occur at sites of inflammation and bacterial infections. In the context of a Pseudomonas aeruginosa infection, we previously demonstrated that acidosis enhances the cellular proinflammatory interleukin (IL)-1β response in vitro. However, how pH alterations affect in vivo IL-1β responses and subsequent IL-1-driven inflammation during infection with P. aeruginosa is unclear. Here, we report that acidosis enhances in vivo IL-1β production and downstream IL-1 receptor-dependent responses during infection with P. aeruginosa in models of acute pneumonia and peritonitis. Importantly, we demonstrate that infection with P. aeruginosa within an acidic environment leads to enhanced production of a subset of proinflammatory cytokines, including chemokine (C-X-C) motif ligand 1, IL-6, and chemokine (C-C motif) ligand 2, and increased neutrophil recruitment. Furthermore, with the use of IL-1 receptor type 1-deficient mice, we identify the contribution of the IL-1 signaling pathway to the acidosis-enhanced inflammatory response and pathology. These data provide insights into the potential benefit of pH regulation during bacterial infections to control disease progression and immunopathology.