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Infection and Immunity, April 2007, p. 1698-1703, Vol. 75, No. 4
0019-9567/07/$08.00+0     doi:10.1128/IAI.01469-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Immunostimulatory Properties of the Emerging Pathogen Stenotrophomonas maltophilia{triangledown}

Valerie J. Waters ,1,{dagger},{ddagger} Marisa I. Gómez,1,{dagger} Grace Soong,1 Sunil Amin,1 Robert K. Ernst,2 and Alice Prince1*

College of Physicians & Surgeons, Columbia University, New York, New York,1 Department of Medicine, University of Washington, Seattle, Washington2

Received 13 September 2006/ Returned for modification 2 November 2006/ Accepted 5 January 2007

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.

* Corresponding author. Mailing address: 650 W. 168th Street, BB 4-416, New York, NY 10032. Phone: (212) 305-4193. Fax: (212) 342-5728. E-mail: asp7{at}columbia.edu.

{triangledown} Published ahead of print on 12 January 2007.

Editor: J. N. Weiser

{dagger} V.J.W. and M.I.G. contributed equally to this work.

{ddagger} Present address: Division of Infectious Diseases, Hospital for Sick Children, Toronto, ON, Canada.

Infection and Immunity, April 2007, p. 1698-1703, Vol. 75, No. 4
0019-9567/07/$08.00+0     doi:10.1128/IAI.01469-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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