RGD Reference Report - Apolipoprotein E-deficient mice have an impaired immune response to Klebsiella pneumoniae. - Rat Genome Database

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Apolipoprotein E-deficient mice have an impaired immune response to Klebsiella pneumoniae.

Authors: De Bont, N  Netea, MG  Demacker, PN  Kullberg, BJ  Van der Meer, JW  Stalenhoef, AF 
Citation: de Bont N, etal., Eur J Clin Invest. 2000 Sep;30(9):818-22.
RGD ID: 11039489
Pubmed: PMID:10998083   (View Abstract at PubMed)

BACKGROUND: All lipoproteins are able to bind to bacterial lipopolysaccharide (LPS), thereby neutralizing its deleterious effects. However, we demonstrated, recently, that in the absence of apolipoprotein E (apoE), eight-fold increased very-low-density lipoprotein levels were not sufficient to protect apoE-deficient (apoE-/-) mice against LPS. During a live Gram-negative infection, mechanisms other than LPS-neutralization may play a role in the pathogenesis of the disease. In the present study we further examined the role of apoE in Gram-negative sepsis. METHODS: Survival, bacterial outgrowth in liver, spleen, kidneys and blood, and tumour necrosis factor-alpha (TNF-alpha) production were measured in apoE-/- mice and control C57BL/6J mice, after an intravenous infection with Klebsiella pneumoniae. RESULTS: Mice that lack apoE showed higher mortality in response to K. pneumoniae than control mice (90% vs. 23% respectively after 2 weeks). ApoE-/- mice had 10-100 times more outgrowth of the bacteria in their organs than controls. Furthermore, circulating TNF-alpha concentrations 90 min after a challenge, were almost twice as high in the apoE-/- mice compared to controls (13.0 +/- 2.9 ng mL-1 vs. 7.6 +/- 3.8 ng mL-1). When apoE-/- and control mice were rendered neutropenic, the discrepancy in survival and outgrowth of K. pneumoniae disappeared. CONCLUSIONS: The apoE-/- mice were more susceptible than control C57BL/6 mice to a K. pneumoniae infection. The absence of apoE may render these mice more susceptible, since this protein is of importance in the detoxification of lipopolysaccharide of Gram-negative bacteria. On the other hand, the phagocytic capacity of granulocytes seems to be decreased in apoE-/- mice, resulting in increased outgrowth and mortality.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Klebsiella Infections severityISOApoe (Mus musculus)11039489; 11039489 RGD 
Klebsiella Infections severityIMP 11039489 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Apoe  (apolipoprotein E)

Genes (Mus musculus)
Apoe  (apolipoprotein E)

Genes (Homo sapiens)
APOE  (apolipoprotein E)


Additional Information