Apolipoprotein E-deficient mice have impaired innate immune responses to Listeria monocytogenes in vivo.
Apolipoprotein E (apoE) influences both innate and acquired immunity in cultured cells. To determine whether apoE affects the immune system in vivo, Listeria monocytogenes (LM) was administered intraperitoneally (10(4) c.f.u.) to congenic C57BL/6 apoE-/- and +/+ mice (n = 12 in each group). Survival was assessed daily for 5 days. Deficiency of apoE significantly increased death by day 5 (P = 0.03). The majority of deaths occurred at day 4. Extent of infection after LM administration was assessed at day 3 by determining colony counts in hepatic and splenic extracts. ApoE+/+ mice had very low colony counts in both spleen and liver [mean +/- SE: 2.0 +/- 0.5 and 0.7 +/- 0.2 (x 10(4)), respectively, n = 8 in each group]; while apoE-/- mice had significantly increased counts in both spleen and liver [64 +/- 51 and 98 +/- 93 (x 10(4)), P = 0.05 and 0.03]. Serum concentrations of TNF-alpha were significantly increased in apoE-/- mice at day 3 compared to apoE+/+ mice (127 +/- 43 pg/ml versus 20 +/- 17, P = 0.003). LM induced more hepatic damage in apoE-/- mice compared to apoE+/+ mice as judged by increased serum concentrations of alanine aminotransferase at day 1 (apoE-/- 301 +/- 45 U/ml, apoE+/+ 101 +/- 9 U/ml, P = 0.01). The increased proliferation and mortality from LM in apoE-/- mice occurred prior to the initiation of acquired immune responses. Therefore, apoE-deficient mice have an impaired innate response to infection by LM.
Roselaar
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Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
Daugherty
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A
D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*; D015169:Colony Count, Microbial; D003433:Crosses, Genetic; D007113:Immunity, Innate / Q000235:genetics; D008089:Listeria monocytogenes / Q000276:immunology* / Q000302:isolation & purification; D008088:Listeriosis / Q000276:immunology* / Q000401:mortality; D008099:Liver / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000382:microbiology
D001057:Apolipoproteins E