Mast cells play an important role in chlamydia pneumoniae lung infection by facilitating immune cell recruitment into the airway

• Published in: The Journal of immunology (1950) 2015-04, Vol.194 (8), p.3840-3851
• Main Authors: Chiba, Norika, Shimada, Kenichi, Chen, Shuang, Jones, Heather D, Alsabeh, Randa, Slepenkin, Anatoly V, Peterson, Ellena, Crother, Timothy R, Arditi, Moshe
• Format: Article
• Language: English
• Subjects: Animals; Anti-Asthmatic Agents - pharmacology; Bronchoalveolar Lavage Fluid; Cell Movement - drug effects; Cell Movement - genetics; Cell Movement - immunology; Chlamydophila Infections - genetics; Chlamydophila Infections - immunology; Chlamydophila Infections - pathology; Chlamydophila pneumoniae; Chlamydophila pneumoniae - immunology; Cromolyn Sodium - pharmacology; Humans; Mast Cells - immunology; Mast Cells - pathology; Matrix Metalloproteinase 9 - genetics; Matrix Metalloproteinase 9 - immunology; Mice; Mice, Transgenic; p-Methoxy-N-methylphenethylamine - pharmacology; Pneumonia, Bacterial - genetics; Pneumonia, Bacterial - immunology; Proteolysis - drug effects
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1402685

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.