Original Article

Apolipoprotein E-deficient mice have impaired innate immune responses to Listeria monocytogenes in vivo

Correspondence to: Alan Daugherty.

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 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 (x10⁴), respectively, n = 8 in each group]; while apoE-/- mice had significantly increased counts in both spleen and liver [64 ± 51 and 98 ± 93 (x10⁴), P = 0.05 and 0.03]. Serum concentrations of TNF- 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, S. E., and A. Daugherty. Apolipoprotein E-deficient mice have impaired innate immune responses to Listeria monocytogenes in vivo. J. Lipid Res. 1998. 39: 1740–1743.

Supplementary key words: macrophages, immunity

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				L. Li, P. A. Thompson, and R. L. Kitchens Infection induces a positive acute phase apolipoprotein E response from a negative acute phase gene: role of hepatic LDL receptors J. Lipid Res., August 1, 2008; 49(8): 1782 - 1793. [Abstract] [Full Text] [PDF]

				G. W. Martens, M. C. Arikan, J. Lee, F. Ren, T. Vallerskog, and H. Kornfeld Hypercholesterolemia Impairs Immunity to Tuberculosis Infect. Immun., August 1, 2008; 76(8): 3464 - 3472. [Abstract] [Full Text] [PDF]

				C. Grunfeld and K. R. Feingold HDL and innate immunity: a tale of two apolipoproteins J. Lipid Res., August 1, 2008; 49(8): 1605 - 1606. [Full Text] [PDF]

				O. M. Kattan, F. B. Kasravi, E. L. Elford, M. T. Schell, and H. W. Harris Apolipoprotein E-Mediated Immune Regulation in Sepsis J. Immunol., July 15, 2008; 181(2): 1399 - 1408. [Abstract] [Full Text] [PDF]

				R. Kleemann, S. Zadelaar, and T. Kooistra Cytokines and atherosclerosis: a comprehensive review of studies in mice Cardiovasc Res, June 9, 2008; (2008) cvn120v2. [Abstract] [Full Text] [PDF]

				P. V. Giannoudis, M. van Griensven, E. Tsiridis, and H. C. Pape The genetic predisposition to adverse outcome after trauma J Bone Joint Surg Br, October 1, 2007; 89-B(10): 1273 - 1279. [Abstract] [Full Text] [PDF]

				P. Krebs, E. Scandella, B. Bolinger, D. Engeler, S. Miller, and B. Ludewig Chronic Immune Reactivity Against Persisting Microbial Antigen in the Vasculature Exacerbates Atherosclerotic Lesion Formation Arterioscler. Thromb. Vasc. Biol., October 1, 2007; 27(10): 2206 - 2213. [Abstract] [Full Text] [PDF]

				R. B. Yates and M. Stafford-Smith The genetic determinants of renal impairment following cardiac surgery. Seminars in Cardiothoracic and Vascular Anesthesia, December 1, 2006; 10(4): 314 - 326. [Abstract] [PDF]

				A. F. Gombart, U. Krug, J. O'Kelly, E. An, V. Vegesna, and H. P. Koeffler Aberrant expression of neutrophil and macrophage-related genes in a murine model for human neutrophil-specific granule deficiency J. Leukoc. Biol., November 1, 2005; 78(5): 1153 - 1165. [Abstract] [Full Text] [PDF]

				K. Ali, M. Middleton, E. Pure, and D. J. Rader Apolipoprotein E Suppresses the Type I Inflammatory Response In Vivo Circ. Res., October 28, 2005; 97(9): 922 - 927. [Abstract] [Full Text] [PDF]

				S. G. Correa, M. C. Rodriguez-Galan, B. Salido-Renteria, R. Cano, H. Cejas, and C. E. Sotomayor High dissemination and hepatotoxicity in rats infected with Candida albicans after stress exposure: potential sensitization to liver damage Int. Immunol., December 1, 2004; 16(12): 1761 - 1768. [Abstract] [Full Text] [PDF]

				D. J. Grainger, J. Reckless, and E. McKilligin Apolipoprotein E Modulates Clearance of Apoptotic Bodies In Vitro and In Vivo, Resulting in a Systemic Proinflammatory State in Apolipoprotein E-Deficient Mice J. Immunol., November 15, 2004; 173(10): 6366 - 6375. [Abstract] [Full Text] [PDF]

				S. Lanza-Jacoby, S. Miller, S. Jacob, D. Heumann, A. G. Minchenko, and J. T. Flynn Hyperlipoproteinemic low-density lipoprotein receptor-deficient mice are more susceptible to sepsis than corresponding wild-type mice Innate Immunity, December 1, 2003; 9(6): 341 - 347. [Abstract] [PDF]

				K. Christopher, T. F. Mueller, R. DeFina, Y. Liang, J. Zhang, R. Gentleman, and D. L. Perkins The graft response to transplantation: a gene expression profile analysis Physiol Genomics, September 29, 2003; 15(1): 52 - 64. [Abstract] [Full Text] [PDF]

				H. W. Harris and F. B. Kasravi Lipoprotein-bound LPS induces cytokine tolerance in hepatocytes Innate Immunity, February 1, 2003; 9(1): 45 - 50. [Abstract] [PDF]

				N. R. Webb, M. A. Bostrom, S. J. Szilvassy, D. R. van der Westhuyzen, A. Daugherty, and F. C. de Beer Macrophage-Expressed Group IIA Secretory Phospholipase A2 Increases Atherosclerotic Lesion Formation in LDL Receptor-Deficient Mice Arterioscler. Thromb. Vasc. Biol., February 1, 2003; 23(2): 263 - 268. [Abstract] [Full Text] [PDF]

				S. Fazio, V. R. Babaev, M. E. Burleigh, A. S. Major, A. H. Hasty, and M. F. Linton Physiological expression of macrophage apoE in the artery wall reduces atherosclerosis in severely hyperlipidemic mice J. Lipid Res., October 1, 2002; 43(10): 1602 - 1609. [Abstract] [Full Text] [PDF]

				U. K. Misra, C. L. Adlakha, G. Gawdi, M. K. McMillian, S. V. Pizzo, and D. T. Laskowitz Apolipoprotein E and mimetic peptide initiate a calcium-dependent signaling response in macrophages J. Leukoc. Biol., October 1, 2001; 70(4): 677 - 683. [Abstract] [Full Text] [PDF]

				B. Ludewig, M. Jaggi, T. Dumrese, K. Brduscha-Riem, B. Odermatt, H. Hengartner, and R. M. Zinkernagel Hypercholesterolemia Exacerbates Virus-Induced Immunopathologic Liver Disease Via Suppression of Antiviral Cytotoxic T Cell Responses J. Immunol., March 1, 2001; 166(5): 3369 - 3376. [Abstract] [Full Text] [PDF]

				D. T. Laskowitz, D. M. Lee, D. Schmechel, and H. F. Staats Altered immune responses in apolipoprotein E-deficient mice J. Lipid Res., April 1, 2000; 41(4): 613 - 620. [Abstract] [Full Text]