Mast cells impair host defense during murine Streptococcus pneumoniae pneumonia.
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.
Center for Experimental and Molecular Medicine Center for Infection and Immunity Amsterdam.
Florry E
FE
van den Boogaard
Center for Experimental and Molecular Medicine Center for Infection and Immunity Amsterdam.
Xanthe
X
Brands
Department of Pathology.
Joris J T H
JJ
Roelofs
Center for Experimental and Molecular Medicine Center for Infection and Immunity Amsterdam.
Regina
R
de Beer
Department of Pathology.
Onno J
OJ
de Boer
Center for Experimental and Molecular Medicine Center for Infection and Immunity Amsterdam.
Cornelis
C
van 't Veer
Center for Experimental and Molecular Medicine Center for Infection and Immunity Amsterdam Division of Infectious Diseases, Academic Medical Center, University of Amsterdam, The Netherlands.
Tom
T
van der Poll
D000818:Animals; D058491:Bacterial Load; D005260:Female; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D008168:Lung / Q000382:microbiology / Q000473:pathology; D008297:Male; D008407:Mast Cells / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011018:Pneumonia, Pneumococcal / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D013296:Streptococcus pneumoniae / Q000276:immunology*
Streptococcus pneumoniae; inflammation; lung; mast cells; pneumonia