Immunostimulatory properties of the emerging pathogen Stenotrophomonas maltophilia

Infect Immun. 2007 Apr;75(4):1698-703. doi: 10.1128/IAI.01469-06. Epub 2007 Jan 12.

Abstract

Stenotrophomonas maltophilia is a multiple-antibiotic-resistant opportunistic pathogen that is being isolated with increasing frequency from patients with health-care-associated infections and especially from patients with cystic fibrosis (CF). While clinicians feel compelled to treat infections involving this organism, its potential for virulence is not well established. We evaluated the immunostimulatory properties and overall virulence of clinical isolates of S. maltophilia using the well-characterized opportunistic pathogen Pseudomonas aeruginosa PAO1 as a control. The properties of CF isolates were examined specifically to see if they have a common phenotype. The immunostimulatory properties of S. maltophilia were studied in vitro by stimulating airway epithelial and macrophage cell lines. A neonatal mouse model of pneumonia was used to determine the rates of pneumonia, bacteremia, and mortality, as well as the inflammatory response elicited by S. maltophilia infection. Respiratory and nonrespiratory S. maltophilia isolates were highly immunostimulatory and elicited significant interleukin-8 expression by airway epithelial cells, as well as tumor necrosis factor alpha (TNF-alpha) expression by macrophages. TNF-alpha signaling appears to be important in the pathogenesis of S. maltophilia infection as less than 20% of TNFR1 null mice (compared with 100% of wild-type mice) developed pneumonia and bacteremia following intranasal inoculation. The S. maltophilia isolates were weakly invasive, and low-level bacteremia with no mortality was observed. Despite the lack of invasiveness of S. maltophilia, the immunostimulatory properties of this organism and its induction of TNF-alpha expression specifically indicate that it is likely to contribute significantly to airway inflammation.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacteremia / microbiology
  • Cell Line
  • Cystic Fibrosis / microbiology
  • Epithelial Cells / immunology
  • Epithelial Cells / microbiology
  • Gram-Negative Bacterial Infections / immunology
  • Gram-Negative Bacterial Infections / microbiology*
  • Gram-Negative Bacterial Infections / mortality
  • Humans
  • Interleukin-8 / biosynthesis
  • Lipid A / immunology
  • Macrophages / immunology
  • Macrophages / microbiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Phagocytosis
  • Pneumonia, Bacterial / microbiology
  • Pseudomonas aeruginosa / immunology
  • Pseudomonas aeruginosa / pathogenicity
  • Receptors, Tumor Necrosis Factor, Type I / deficiency
  • Receptors, Tumor Necrosis Factor, Type I / immunology
  • Respiratory Mucosa / microbiology
  • Respiratory Tract Infections / immunology
  • Respiratory Tract Infections / microbiology*
  • Stenotrophomonas maltophilia / immunology*
  • Stenotrophomonas maltophilia / pathogenicity*
  • Tumor Necrosis Factor-alpha / biosynthesis

Substances

  • Interleukin-8
  • Lipid A
  • Receptors, Tumor Necrosis Factor, Type I
  • Tnfrsf1a protein, mouse
  • Tumor Necrosis Factor-alpha