Mast cells modulate pulmonary acute inflammation and host defense in a murine model of tuberculosis.
BACKGROUND
Mast cells (MCs) participate in host resistance to several pathogens, but little is known about the role played by MCs in Mycobacterium tuberculosis infection.


METHODS
Compound 48/80 (C48/80)-treated mice and nontreated mice were infected intratracheally with 1 x 10(5) viable M. tuberculosis bacilli (MTB; strain H37Rv).


RESULTS
Infected BALB/c mice developed an acute pulmonary inflammation and had higher levels of tumor necrosis factor- alpha , interleukin-1, keratinocyte-derived chemokine, monocyte chemotactic protein-1, and macrophage inflammatory protein-2 in the lungs by day 15. In vivo degranulation of MCs by C48/80 led to a reduction in the inflammatory reaction that was associated with a marked decline in lung proinflammatory cytokine and chemokine levels. The magnitude of the cellular immune response was also partially impaired in infected mice treated with C48/80. The number of Mycobacteria bacilli recovered from the lungs of infected mice treated with C48/80 was 1 log higher than that recovered from untreated infected mice. C48/80 treatment attenuated the granulomatous inflammation in the lung parenchyma seen in untreated MTB-infected mice.


CONCLUSIONS
These findings suggest that MCs participate in host defense against M. tuberculosis infection through the production and secretion of cytokines and chemokines that play a role in the recruitment and activation of inflammatory cells in this experimental model.
Carlos
Daniela
D
Departamento de Análises Clínicas, Toxicológicas, e Bromatologicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Ribeirão Preto, SP, Brazil.
de Souza Júnior
Devandir Antonio
DA
de Paula
Lúcia
L
Jamur
Maria Célia
MC
Oliver
Constance
C
Ramos
Simone Gusmão
SG
Silva
Célio Lopes
CL
Faccioli
Lúcia Helena
LH
D000818:Animals; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D006099:Granuloma; D007249:Inflammation / Q000473:pathology*; D007962:Leukocytes / Q000187:drug effects; D008168:Lung / Q000166:cytology / Q000473:pathology*; D008407:Mast Cells / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018417:Th1 Cells / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism; D014397:Tuberculosis, Pulmonary / Q000276:immunology*; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
D016207:Cytokines; D003189:p-Methoxy-N-methylphenethylamine