Ornithine decarboxylase regulates M1 macrophage activation and mucosal inflammation via histone modifications

• DOI: 10.1073/pnas.1614958114
• Publication Date: 2017-01-18T03:01:19Z
• Authors: Dana M. Hardbower; Mohammad Asim; Paula B. Luis; Kshipra Singh; Daniel P. Barry; Chunying Yang; Meredith A. Steeves; John L. Cleveland; Claus Schneider; M. Blanca Piazuelo; Alain P. Gobert; Keith T. Wilson
• Keywords: Male; 0301 basic medicine; Helicobacter pylori; Colon; Macrophages; Enterobacteriaceae Infections; Macrophage Activation; Colitis; Ornithine Decarboxylase; Cell Line; Helicobacter Infections; 3. Good health; Histones; Mice; 03 medical and health sciences; Gastric Mucosa; Gastritis; NLR Family, Pyrin Domain-Containing 3 Protein; Putrescine; Animals; Citrobacter rodentium; Cytokines; Humans

SignificanceThe pathogenesis of many bacteria is enhanced by the ability to establish persistent infection. Macrophages, particularly classically activated M1 macrophages, provide essential functions in the initiation of antibacterial immune responses. The regulation of macrophage activation is still poorly understood. Here, we demonstrate that ornithine decarboxylase (ODC), the rate-limiting enzyme in polyamine synthesis, regulates M1 activation duringHelicobacter pyloriandCitrobacter rodentiuminfection. Deletion ofOdcin macrophages resulted in increased inflammation and decreased bacterial persistence in mouse models. The enhanced M1 response was due to alterations in histone modifications, resulting in changes in chromatin structure and up-regulated transcription. These findings represent a novel mechanism by which ODC directly regulates macrophage activation and provides new insights into understanding bacterial persistence.