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 (10⁴ c.f.u.) to congenic C57BL/6 apoE -/- and +/+ mice (n = 12 in each group). Survival was assessed dally 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 10⁴), respectively, n = 8 in each group]; while apoE-/mice had significantly increased counts in both spleen and liver [64 ± 51 and 98 ± 93 (x 10⁴), P = 0.05 and 0.03]. Serum concentrations of TNF-α 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.