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Infect. Immun. doi:10.1128/IAI.00601-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Role of CD14 in responses to clinical isolates of Escherichia coli: effects of K1 capsule expression

Department of Microbiology and Immunology, CUNY Medical School, Sophie Davis School for Biomedical Sciences, City College of New York, New York; Center of Immunology and Inflammation, Laboratory of Innate Immunity, The Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health Systems, Manhasset, New York; Ecologie et évolution des micro-organismes, INSERM U722, Faculté de Médecine Xavier Bichat, Paris, France; Division of Infectious Diseases, Department of Pediatrics, Johns Hopkins School of Medicine, Baltimore, Maryland

^* To whom correspondence should be addressed. Email: sgoyert{at}med,.cuny.edu.

	Abstract

Severe bacterial infections leading to sepsis/septic shock can be induced by bacteria that utilize different factors to drive pathogenicity and/or virulence leading to disease in the host. One major factor expressed by all clinical isolates of Gram-negative bacteria is LPS; a second factor expressed by some Escherichia coli is a K1-polysaccharide capsule. To determine the role of the CD14 LPS receptor in the pathogenic effects of naturally occurring E. coli, the responses of CD14-/- and CD14+/+ mice to three different isolates of E. coli obtained from sepsis patients were compared; two isolates express both smooth LPS and the K1 antigen while the third isolate expresses only LPS and is negative for K1. An additional K1-positive isolate obtained from a newborn with meningitis, and its K1-negative isogenic mutant, were also used for these studies. CD14-/- mice were resistant to the lethal effects of the K1-negative isolates. This resistance was accompanied by significantly lower levels of systemic TNF and IL-6 compared to CD14+/+ mice, enhanced clearance of the bacteria, and significantly fewer additional gross symptoms. In contrast, CD14-/- mice were as sensitive as CD14+/+ mice to the lethal effects of the K1-positive isolates, even though they had significantly lower levels of TNF and IL-6 than CD14+/+ mice. These studies show that different bacterial isolates can use distinctly different mechanisms to cause disease and suggest that new, non-antibiotic therapeutics will need to be directed against multiple targets.