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

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...

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Bibliographic Details
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
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Summary: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.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.1402685