Mast cells modulate pulmonary acute inflammation and host defense in a murine model of tuberculosis

J Infect Dis. 2007 Nov 1;196(9):1361-8. doi: 10.1086/521830. Epub 2007 Oct 1.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cytokines / metabolism
  • Disease Models, Animal
  • Granuloma
  • Inflammation / pathology*
  • Leukocytes / drug effects
  • Lung / cytology
  • Lung / pathology*
  • Mast Cells / physiology*
  • Mice
  • Mice, Inbred BALB C
  • Th1 Cells / metabolism
  • Th2 Cells / metabolism
  • Tuberculosis, Pulmonary / immunology*
  • p-Methoxy-N-methylphenethylamine / pharmacology

Substances

  • Cytokines
  • p-Methoxy-N-methylphenethylamine