Published ahead of print on October 6, 2005, doi:10.1164/rccm.200507-1034OC
© 2006 American Thoracic Society doi: 10.1164/rccm.200507-1034OC
Mast Cells Protect Mice from Mycoplasma PneumoniaCardiovascular Research Institute, Comprehensive Cancer Institute, and Departments of Medicine, Anatomy, Microbiology and Immunology, and Pediatrics, University of California at San Francisco; Northern California Institute for Research and Education; and Veterans Affairs Medical Center, San Francisco, California Correspondence and requests for reprints should be addressed to George H. Caughey, M.D., Pulmonary and Critical Care Medicine, Mailstop 111-D, Veterans Affairs Medical Center, 4150 Clement Street, San Francisco, CA 94121. E-mail: george.caughey{at}uscf.edu Rationale: As the smallest free-living bacteria and a frequent cause of respiratory infections, mycoplasmas are unique pathogens. Mice infected with Mycoplasma pulmonis can develop localized, life-long airway infection accompanied by persistent inflammation and remodeling. Objective: Because mast cells protect mice from acute septic peritonitis and gram-negative pneumonia, we hypothesized that they defend against mycoplasma infection. This study tests this hypothesis using mast cell–deficient mice. Methods: Responses to airway infection with M. pulmonis were compared in wild-type and mast cell–deficient KitW-sh/KitW-sh mice and sham-infected control mice. Measurements and Main Results: Endpoints include mortality, body and lymph node weight, mycoplasma antibody titer, and lung mycoplasma burden and histopathology at intervals after infection. The results reveal that infected KitW-sh/KitW-sh mice, compared with other groups, lose more weight and are more likely to die. Live mycoplasma burden is greater in KitW-sh/KitW-sh than in wild-type mice at early time points. Four days after infection, the difference is 162-fold. Titers of mycoplasma-specific IgM and IgA appear earlier and rise higher in KitW-sh/KitW-sh mice, but antibody responses to heat-killed mycoplasma are not different compared with wild-type mice. Infected KitW-sh/KitW-sh mice develop larger bronchial lymph nodes and progressive pneumonia and airway occlusion with neutrophil-rich exudates, accompanied by angiogenesis and lymphangiogenesis. In wild-type mice, pneumonia and exudates are less severe, quicker to resolve, and are not associated with increased angiogenesis. Conclusions: These findings suggest that mast cells are important for innate immune containment of and recovery from respiratory mycoplasma infection.
Key Words: angiogenesis • bronchitis • innate immunity • lymphangiogenesis • pneumonia This article has been cited by other articles:
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