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Mast cells impair host defense during murine Streptococcus pneumoniae pneumonia
Florry E van den Boogaard1, Xanthe Brands1, Joris J T H Roelofs2
1Center for Experimental and Molecular Medicine Center for Infection and Immunity Amsterdam.
Background:
Streptococcus pneumoniae is the most common causative pathogen in community-acquired pneumonia. Mast cells (MCs) are located mainly at the host-environment interface where they function as sentinels.
Objective:
Our goal was to study the role of MCs during pneumonia caused by S. pneumoniae.
Methods:
Lung tissue of patients who had died from pneumococcal pneumonia or a nonpulmonary cause was stained for MCs and tryptase. Wild-type (WT) and MC-deficient (Kit(W-sh/W-sh)) mice were observed or sacrificed after induction of pneumonia by intranasal inoculation of S. pneumoniae. In separate experiments, WT mice were treated with doxantrazole or cromoglycate, which are MC stabilizing agents.
Results:
The constitutive presence of tryptase-positive MCs was reduced in affected lungs from pneumonia patients. Kit(W-sh/W-sh) mice showed a prolonged survival during the first few days after median lethal dose (LD)100 and LD50 infection, while overall mortality did not differ from that in WT mice. Relative to WT mice, Kit(W-sh/W-sh) mice showed reduced bacterial counts with less bacterial dissemination to distant organs and less inflammation. Neither doxantrazole nor cromoglycate influenced antibacterial defense or inflammatory responses after airway infection with S. pneumoniae.
Conclusions:
MCs exhibit an unfavorable role in host defense during pneumococcal pneumonia by a mechanism independent of degranulation.
Insights
Mast cells (MCs) play an unfavorable role in host defense against Streptococcus pneumoniae pneumonia. MC deficiency improved survival and reduced bacterial spread in mice, independent of degranulation.
Area of Science:
- Immunology
- Microbiology
- Pathology
Background:
- Streptococcus pneumoniae is a leading cause of community-acquired pneumonia.
- Mast cells (MCs) act as sentinels at host-environment interfaces.
Purpose of the Study:
- To investigate the role of mast cells (MCs) in host defense during Streptococcus pneumoniae pneumonia.
Main Methods:
- Examined lung tissue from pneumonia patients for mast cells and tryptase.
- Utilized wild-type (WT) and mast cell-deficient (Kit(W-sh/W-sh)) mice infected with S. pneumoniae.
- Administered mast cell stabilizers (doxantrazole, cromoglycate) to WT mice.
Main Results:
- Reduced tryptase-positive MCs observed in human pneumonia lung tissue.
- MC-deficient mice exhibited prolonged survival, reduced bacterial counts, and less inflammation.
- MC stabilizers did not affect antibacterial defense or inflammation in mice.
Conclusions:
- Mast cells (MCs) have a detrimental role in host defense against pneumococcal pneumonia.
- This unfavorable role is independent of mast cell degranulation.
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