SP-A preserves airway homeostasis during Mycoplasma pneumoniae infection in mice

J Immunol. 2009 Jun 15;182(12):7818-27. doi: 10.4049/jimmunol.0900452.

Abstract

The lung is constantly challenged during normal breathing by a myriad of environmental irritants and infectious insults. Pulmonary host defense mechanisms maintain homeostasis between inhibition/clearance of pathogens and regulation of inflammatory responses that could injure the airway epithelium. One component of this defense mechanism, surfactant protein-A (SP-A), exerts multifunctional roles in mediating host responses to inflammatory and infectious agents. SP-A has a bacteriostatic effect on Mycoplasma pneumoniae (Mp), which occurs by binding surface disaturated phosphatidylglycerols. SP-A can also bind the Mp membrane protein, MPN372. In this study, we investigated the role of SP-A during acute phase pulmonary infection with Mp using mice deficient in SP-A. Biologic responses, inflammation, and cellular infiltration, were much greater in Mp infected SP-A(-/-) mice than wild-type mice. Likewise, physiologic responses (airway hyperresponsiveness and lung compliance) to Mp infection were more severely affected in SP-A(-/-) mice. Both Mp-induced biologic and physiologic changes were attenuated by pharmacologic inhibition of TNF-alpha. Our findings demonstrate that SP-A is vital to preserving lung homeostasis and host defense to this clinically relevant strain of Mp by curtailing inflammatory cell recruitment and limiting an overzealous TNF-alpha response.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Bronchoalveolar Lavage
  • Homeostasis / immunology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mycoplasma pneumoniae / physiology*
  • Pneumonia, Mycoplasma / genetics
  • Pneumonia, Mycoplasma / immunology*
  • Pneumonia, Mycoplasma / metabolism
  • Pneumonia, Mycoplasma / pathology*
  • Pulmonary Surfactant-Associated Protein A / deficiency
  • Pulmonary Surfactant-Associated Protein A / genetics
  • Pulmonary Surfactant-Associated Protein A / metabolism*
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Tumor Necrosis Factor-alpha / immunology

Substances

  • Pulmonary Surfactant-Associated Protein A
  • Tumor Necrosis Factor-alpha