title: Housing conditions modulate the severity of Mycoplasma pulmonis infection in mice deficient in class A scavenger receptor.
abstract: Mycoplasmosis is a frequent causative microbial agent of community-acquired pneumonia and has been linked to exacerbation of chronic obstructive pulmonary disease. The macrophage class A scavenger receptor (SRA) facilitates the clearance of noxious particles, oxidants, and infectious organisms by alveolar macrophages. We examined wildtype and SRA(-/-) mice, housed in either individually ventilated or static filter-top cages that were cycled with fresh bedding every 14 d, as a model of gene-environment interaction on the outcome of pulmonary Mycoplasma pulmonis infection. Intracage NH3 gas measurements were recorded daily prior to infection. Mice were intranasally infected with 1 × 10(7) cfu M. pulmonis UAB CT and evaluated at 3, 7, and 14 d after inoculation. Wildtype mice cleared 99.5% of pulmonary M. pulmonis by 3 d after infection but remained chronically infected through the study. SRA (-/-) mice were chronically infected with 40-fold higher mycoplasma numbers than were wildtype mice. M. pulmonis caused a chronic mixed inflammatory response that was accompanied with high levels of IL1β, KC, MCP1, and TNFα in SRA(-/-) mice, whereas pulmonary inflammation in WT mice was represented by a monocytosis with elevation of IL1β. Housing had a prominent influence on the severity and persistence of mycoplasmosis in SRA(-/-) mice. SRA(-/-) mice housed in static cages had an improved recovery and significant changes in surfactant proteins SPA and SPD compared with baseline levels. These results indicate that SRA is required to prevent chronic mycoplasma infection of the lung. Furthermore, environmental conditions may exacerbate chronic inflammation in M. pulmonis-infected SRA(-/-) mice.
authors.affiliation: Department of Comparative Medicine, Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Booth
authors.affiliation: Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA.
authors.forename: Todd M
authors.initials: TM
authors.lastname: Umstead
authors.affiliation: Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA.
authors.forename: Sanmei
authors.initials: S
authors.lastname: Hu
authors.affiliation: Department of Genetics, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Kevin F
authors.initials: KF
authors.lastname: Dybvig
authors.affiliation: Department of Comparative Medicine, Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA; Department of Pathology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA.
authors.forename: Timothy K
authors.initials: TK
authors.lastname: Cooper
authors.affiliation: Department of Comparative Medicine, Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA.
authors.forename: Ronald P
authors.initials: RP
authors.lastname: Wilson
authors.affiliation: Department of Pediatrics, Department of Microbiology and Immunology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA. zchroneos@hmc.psu.edu.
authors.forename: Zissis C
authors.initials: ZC
authors.lastname: Chroneos
mesh_terms: D016902:Air Pollution, Indoor / Q000032:analysis; D000641:Ammonia / Q000032:analysis; D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D018932:Chemokine CCL2 / Q000097:blood; D018925:Chemokines / Q000097:blood; D004591:Electrophoresis, Polyacrylamide Gel; D006799:Housing, Animal / Q000592:standards*; D053583:Interleukin-1beta / Q000097:blood; D051379:Mice; D018345:Mice, Knockout; D009175:Mycoplasma Infections / Q000378:metabolism / Q000473:pathology*; D045803:Mycoplasma pulmonis / Q000472:pathogenicity*; D051117:Scavenger Receptors, Class A / Q000172:deficiency* / Q000235:genetics; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D018932:Chemokine CCL2; D018925:Chemokines; D053583:Interleukin-1beta; D051117:Scavenger Receptors, Class A; D014409:Tumor Necrosis Factor-alpha; C074302:keratinocyte-derived chemokines; D000641:Ammonia