Role of CD14 in responses to clinical isolates of Escherichia coli: effects of K1 capsule expression.
Severe bacterial infections leading to sepsis or 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 lipopolysaccharide (LPS); a second factor expressed by some Escherichia coli strains 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 a K1-negative isogenic mutant of this strain 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 tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) in these mice than in 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-alpha 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, nonantibiotic therapeutics need to be directed against multiple targets.
Metkar
Shalaka
S
Department of Microbiology and Immunology, CUNY Medical School, and Sophie Davis School for Biomedical Sciences, City College of New York, New York, New York, USA.
Awasthi
Shanjana
S
Denamur
Erick
E
Kim
Kwang Sik
KS
Gangloff
Sophie C
SC
Teichberg
Saul
S
Haziot
Alain
A
Silver
Jack
J
Goyert
Sanna M
SM
D000825:Animal Structures / Q000382:microbiology; D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology*; D016667:Bacterial Capsules / Q000235:genetics / Q000276:immunology*; D015169:Colony Count, Microbial; D004198:Disease Susceptibility; D004926:Escherichia coli / Q000276:immunology* / Q000302:isolation & purification; D004927:Escherichia coli Infections / Q000382:microbiology / Q000401:mortality / Q000503:physiopathology; D017353:Gene Deletion; D007113:Immunity, Innate / Q000235:genetics; D015850:Interleukin-6 / Q000097:blood; D018950:Lipopolysaccharide Receptors / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D011135:Polysaccharides, Bacterial / Q000235:genetics / Q000276:immunology*; D018805:Sepsis / Q000382:microbiology; D016019:Survival Analysis; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D000942:Antigens, Bacterial; D015850:Interleukin-6; D018950:Lipopolysaccharide Receptors; D011135:Polysaccharides, Bacterial; D014409:Tumor Necrosis Factor-alpha; C036962:capsular polysaccharide K1
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