title: Mast cells play an important role in chlamydia pneumoniae lung infection by facilitating immune cell recruitment into the airway.
abstract: Mast cells are known as central players in allergy and anaphylaxis, and they play a pivotal role in host defense against certain pathogens. Chlamydia pneumoniae is an important human pathogen, but it is unclear what role mast cells play during C. pneumoniae infection. We infected C57BL/6 (wild-type [WT]) and mast cell-deficient mice (Kit(W-sh/W-sh) [Wsh]) with C. pneumoniae. Wsh mice showed improved survival compared with WT mice, with fewer cells in Wsh bronchoalveolar lavage fluid (BALF), despite similar levels of cytokines and chemokines. We also found a more rapid clearance of bacteria from the lungs of Wsh mice compared with WT mice. Cromolyn, a mast cell stabilizer, reduced BALF cells and bacterial burden similar to the levels seen in Wsh mice; conversely, Compound 48/80, a mast cell degranulator, increased the number of BALF cells and bacterial burden. Histology showed that WT lungs had diffuse inflammation, whereas Wsh mice had patchy accumulations of neutrophils and perivascular accumulations of lymphocytes. Infected Wsh mice had reduced amounts of matrix metalloprotease-9 in BALF and were resistant to epithelial integral membrane protein degradation, suggesting that barrier integrity remains intact in Wsh mice. Mast cell reconstitution in Wsh mice led to enhanced bacterial growth and normal epithelial integral membrane protein degradation, highlighting the specific role of mast cells in this model. These data suggest that mast cells play a detrimental role during C. pneumoniae infection by facilitating immune cell infiltration into the airspace and providing a more favorable replicative environment for C. pneumoniae.
authors.affiliation: Division of Pediatric Infectious Diseases and Immunology, Department of Biomedical Sciences, Cedars-Sinai Medical Center and David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90048;
authors.forename: Norika
authors.initials: N
authors.lastname: Chiba
authors.affiliation: Division of Pediatric Infectious Diseases and Immunology, Department of Biomedical Sciences, Cedars-Sinai Medical Center and David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90048;
authors.forename: Kenichi
authors.initials: K
authors.lastname: Shimada
authors.affiliation: Division of Pediatric Infectious Diseases and Immunology, Department of Biomedical Sciences, Cedars-Sinai Medical Center and David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90048;
authors.forename: Shuang
authors.initials: S
authors.lastname: Chen
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, Cedars-Sinai Medical Center and David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90048;
authors.forename: Heather D
authors.initials: HD
authors.lastname: Jones
authors.affiliation: Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center and David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90048; and.
authors.forename: Randa
authors.initials: R
authors.lastname: Alsabeh
authors.affiliation: Department of Pathology, University of California Irvine, Irvine, CA 92697.
authors.forename: Anatoly V
authors.initials: AV
authors.lastname: Slepenkin
authors.affiliation: Department of Pathology, University of California Irvine, Irvine, CA 92697.
authors.forename: Ellena
authors.initials: E
authors.lastname: Peterson
authors.affiliation: Division of Pediatric Infectious Diseases and Immunology, Department of Biomedical Sciences, Cedars-Sinai Medical Center and David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90048;
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Crother
authors.affiliation: Division of Pediatric Infectious Diseases and Immunology, Department of Biomedical Sciences, Cedars-Sinai Medical Center and David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90048; moshe.arditi@cshs.org.
authors.forename: Moshe
authors.initials: M
authors.lastname: Arditi
mesh_terms: D000818:Animals; D018927:Anti-Asthmatic Agents / Q000494:pharmacology; D001992:Bronchoalveolar Lavage Fluid; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D023521:Chlamydophila Infections / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D016993:Chlamydophila pneumoniae / Q000276:immunology*; D004205:Cromolyn Sodium / Q000494:pharmacology; D006801:Humans; D008407:Mast Cells / Q000276:immunology* / Q000473:pathology; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D018410:Pneumonia, Bacterial / Q000235:genetics / Q000276:immunology*; D059748:Proteolysis / Q000187:drug effects; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
chemical_list: D018927:Anti-Asthmatic Agents; D003189:p-Methoxy-N-methylphenethylamine; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse; D004205:Cromolyn Sodium