Published ahead of print on October 6, 2005, doi:10.1164/rccm.200507-1034OC Am. J. Respir. Crit. Care Med., Volume 173, Number 2, January 2006, 219-225 A more recent version of this article appeared on January 15, 2006
Submitted on July 5, 2005 Mast Cells Protect Mice From Mycoplasma PneumoniaXiang Xu1,1 Cardiovascular Research Institute, University of California at San Francisco, San Francisco, CA, USA, 2 Department of Microbiology and Immunology, University of California at San Francisco, San Francisco, CA, USA, 3 Department of Anatomy, University of California at San Francisco, San Francisco, CA, USA, 4 Department of Medicine, University of California at San Francisco, San Francisco, CA, USA, 5 Cardiovascular Research Institute, University of California at San Francisco, San Francisco, CA, USA; Comprehensive Cancer Institute, University of California at San Francisco, San Francisco, CA, USA; Department of Anatomy, University of California at San Francisco, San Francisco, CA, USA, 6 Cardiovascular Research Institute, University of California at San Francisco, San Francisco, CA, USA; Comprehensive Cancer Institute, University of California at San Francisco, San Francisco, CA, USA, 7 Cardiovascular Research Institute, University of California at San Francisco, San Francisco, CA, USA; Comprehensive Cancer Institute, University of California at San Francisco, San Francisco, CA, USA; Northern California Institute of Research and Education, Veterans Affairs Medical Center, San Francisco, CA, USA * To whom correspondence should be addressed. E-mail: ghc{at}itsa.ucsf.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, with sham-infected mice as controls. 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 to 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 to wild-type animals. Infected KitW-sh/KitW-sh animals 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: Innate immunity, angiogenesis, lymphangiogenesis, pneumonia, bronchitis
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