title: Induction of cyclooxygenase-2 signaling by Stomatococcus mucilaginosus highlights the pathogenic potential of an oral commensal.
abstract: Stomatococcus mucilaginosus is an oral commensal that has been occasionally reported to cause severe infections in immunocompromised patients. There is no information about the pathogenic role of S. mucilaginosus in airway infections. In a cohort of 182 subjects with bronchiectasis, we found that 9% were colonized with S. mucilaginosus in their lower airways by culture growth from bronchoalveolar lavage. To address the pathogenic potential of S.mucilaginosus, we developed a murine model of S. mucilaginosus lung infection. Intratracheal injection of S. mucilaginosus in C57BL/6 mice resulted in a neutrophilic influx with production of proinflammatory cytokines, chemokines, and lipid mediators, mainly PGE₂ with induction of cyclooxygenase-2 (COX-2) in the lungs. Presence of TLR2 was necessary for induction of COX-2 and production of PGE₂ by S. mucilaginosus. TLR2-deficient mice showed an enhanced clearance of S. mucilaginosus compared with wild-type mice. Administration of PGE₂ to TLR2(-/-) mice resulted in impaired clearance of S. mucilaginosus, suggesting a key role for COX-2-induced PGE₂ production in immune response to S. mucilaginosus. Mechanistically, induction of COX-2 in macrophages was dependent on the p38-ERK/MAPK signaling pathway. Furthermore, mice treated with S. mucilaginosus and Pseudomonas aeruginosa showed an increased mortality compared with mice treated with PA103 or S. mucilaginosus alone. Inhibition of COX-2 significantly improved survival in mice infected with PA103 and S. mucilaginosus. These data provide novel insights into the bacteriology and personalized microbiome in patients with bronchiectasis and suggest a pathogenic role for S. mucilaginosus in patients with bronchiectasis.
authors.affiliation: Veterans Affairs Medical Center, Gainesville, FL 32610;
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Yuan
authors.forename: Dipti
authors.initials: D
authors.lastname: Panchal
authors.forename: Mansoor Ali
authors.initials: MA
authors.lastname: Syed
authors.forename: Hiren
authors.initials: H
authors.lastname: Mehta
authors.forename: Myungsoo
authors.initials: M
authors.lastname: Joo
authors.forename: Walid
authors.initials: W
authors.lastname: Hadid
authors.forename: Ruxana T
authors.initials: RT
authors.lastname: Sadikot
mesh_terms: D000818:Animals; D001987:Bronchiectasis / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000096:biosynthesis; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D020935:MAP Kinase Signaling System; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008835:Micrococcaceae / Q000276:immunology / Q000472:pathogenicity*; D020556:Neutrophil Infiltration / Q000276:immunology; D011014:Pneumonia / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology* / Q000401:mortality; D011550:Pseudomonas aeruginosa / Q000276:immunology / Q000472:pathogenicity; D012307:Risk Factors; D015398:Signal Transduction; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism
chemical_list: D016861:Cyclooxygenase Inhibitors; D051195:Toll-Like Receptor 2; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D015232:Dinoprostone