Impairment of Host Resistance toListeria monocytogenesInfection in Liver ofdb/dbandob/obMice
Tóm tắt
Leptin is an adipocyte-derived hormone that regulates a number of physiological functions, including energy homeostasis and immune function. In immune responses, leptin plays a role in the induction of inflammation. We investigated a role of leptin in Listeria monocytogenes infection using leptin receptor–deficient db/db mice and leptin-deficient ob/ob mice. These mutant mice were highly susceptible to L. monocytogenes, and the elimination of bacteria from the liver was inhibited. After infection, the induction of monocyte chemoattractant protein-1 (MCP-1) and KC mRNA in the liver of db/db mice and the MCP-1 mRNA expression in the liver of ob/ob mice was decreased compared with their heterozygote littermates. Leptin replacement in ob/ob mice resulted in improvement of anti-listerial resistance and the MCP-1 mRNA expression. The elimination of L. monocytogenes was significantly enhanced, and the expression of MCP-1 and KC mRNA was completely reversed in db/db mice by insulin treatment. These results suggest that leptin is required for host resistance to L. monocytogenes infection and that hyperglycemia caused by leptin deficiency is involved in the inefficient elimination of bacteria from the liver. Moreover, defect of MCP-1 expression in the liver may be involved in the attenuated host resistance in these mutant mice.
Từ khóa
Tài liệu tham khảo
Zhang Y, Proenca R, Maffel M, Barone M, Leopold L, Friedman JM: Positional cloning of the mouse obese gene and its human homologue. Nature 372:425–432,1994
Halaas JL, Gajiwals KS, Maffei M, Cohen SL, Chait BT, Rabinowitz D, Lallone RL, Burley SK, Friedman JM: Weight-reducing effects of the plasma protein encoded by the obese gene. Science 269:543–546,1995
Chen H, Charlat O, Tartaglia LA, Woolf EA, Weng X, Ellis SJ, Lakey ND, Culpepper J, Moore KJ, Breitbart RE, Duyk GM, Tepper RI, Morgenstem JP: Evidence that the diabetes gene encodes the leptin receptor: identification of a mutation in the leptin receptor gene in db/db mice. Cell 84:491–495,1996
Coleman DL: Obese and diabetes: two mutant genes causing diabetes-obesity syndromes in mice. Diabetologia 14:141–148,1978
Ahima RS, Saper CB, Flier JS, Elmquist JK: Leptin regulation of neuroendocrine systems. Front Neuroendocrinol 21:263–307,2000
Fantussi G, Faggioni R: Leptin in the regulation of immunity, inflammation, and hematopoiesis. J Leukoc Biol 68:437–446,2000
Lord GM, Matarese G, Howard JK, Baker RJ, Bloom SR, Lechler RI: Leptin modulates the T-cell immune response and reverses starvation-induced immunosuppression. Nature 394:897–901,1998
Matarese G, Di Giacomo A, Sanna V, Lord GM, Howard JK, Di Tuoro A, Bloom SR, Lechler RI, Zappacosta S, Fontana S: Requirement for leptin in the induction and progression of autoimmune encephalomyelitis. J Immunol 166:5909–5916,2001
Busso N, So A, Chobaz-Peclat V, Morard C, martinez-Soria E, Talabot-Ayer, Gabay C: Leptin signaling deficiency impairs humoral and cellular immune responses and attenuates experimental arthritis. J Immunol 168:875–882,2002
Caldefie-Chezet F, Poulin A, Tridon A, Sion B, Vasson M-P: Leptin: a potential regulator of polymorphonuclear neutrophil bactericidal action?J Leukoc Biol 69:414–418,2001
Mancuso P, Gottschalk A, Phare SM, Peters-Golden M, Lukacs NW, Huffnagle GB: Leptin-decifient mice exhibit impaired host defense in Gram-negative pneumonia. J Immunol 168:4018–4024,2002
Moore SI, Huffnagel GB, Chen G-H, White ES, Mancuso P: Leptin modulates neutrophil phagocytosis of Klebsiella pneumoniae. Infect Immun 71:4182–4185,2003
Rayfield EJ, Ault MJ, Keusch GT, Brothers MJ, Nechemias C, Smith H: Infection and diabetes: the case for glucose control. Am J Med 72:439–450,1982
Joshi N, Caputo GM, Weitekamp MR, Karchmer AW: Infections in patients with diabetes mellitus. N Engl J Med 341:1906–1912,1999
Skogberg K, Syrjanen J, Jahkola M, Renkonen OV, Paavonen J, Ahonen J, Kontiainen S, Ruutu P, Valtonen V: Clinical presentation and outcome of listeriosis in patients with and without immnosuppressive therapy. Clin Infect Dis 14:815–821,1992
Hsieh C-S, Macatonis SE, Tripp CS, Wolf SF, O’Garra A, Murphy KM: Development of Th1 CD4+ T-cells through IL-12 produced by Listeria-induced macrophages. Science 260:547–549,1993
Buchmeier NA, Schreiber RD: Requirement of endogenous interferon-γ for resolution of Listeria monocytogenes infection. Proc Natl Acad Sci U S A 82:7404–7408,1985
Huang S, Hendriks W, Althage A, Hemmi S, Bluthmann H, Kamijo R, Vilcek J, Zinkernagel RM, Aguet M: Immune response in mice that lack the intereferon-γ receptor. Science 259:1742–1745,1993
Conlan JW, North RJ: Neutrophils are essential for early anti-Listeria defense in the liver, but not in the spleen or peritoneal cavity, as revealed by a granulocyte-depleting monoclonal antibody. J Exp Med 179:259–268,1994
Luster AD: Chemokines: chemotactic cytokines that mediate inflammation. N Engl J Med 338:436–445,1998
Kurihara T, Warr G, Loy J, Bravo R: Defects in macrophage recruitment and host defense in mice lacking the CCR2 chemokine receptor. J Exp Med 186:1757–1762,1997
Czuprynski CJ, Brown JF, Steinberg H, Carroll D: Mice lacking the murine interleukin-8 receptor homologue demonstrate paradoxical responses to acute and chronic experimental infection with Listeria monocytogenes. Microb Pathog 24:17–23,1998
Chensue SW: Molecular machinations: chemokine signals in host-pathogen interactions. Clin Microbiol Rev 14:821–835,2001
Nakane A, Minagawa T, Kohanawa M, Chen Y, Sato H, Moriyama M, Tsuruoka N: Interactions between endogenous gamma interferon and tumor necrosis factor in host resistance against primary and secondary Listeria monocytogenes infections. Infect Immun 57:3331–3337,1989
Chomczynski P, Sacci N: Single step method for RNA isolation by acid guanidium thiocyanate-phenol-chloroform extraction. Anal Biochem 162:156–159,1987
Ishida Y, Konda T, Ohshima T, Fujiwara H, Iwakura Y, Mukaida N: A pivotal involvement of IFN-γ in the pathogenesis of acetaminophen-induced acute liver injury. FASEB J 16:1227–1236,2002
Yang S, Lin H, Diehl AM: Fatty liver vulnerability to endotoxin-induced damage despite NF-κB induction and inhibited caspase 3 activity. Am J Physiol Gastrointest Liver Physiol 281:G382–G392,2001
Sasaki T, Mieno M, Udono H, Yamaguchi K, Usui T, Hara K, Shiku H, Nakayama E: Roles of CD4+ and CD8+ cells, and the effect of administration of recombinant murine interferon γ in listerial infection. J Exp Med 171:1141–1154,1990
Gregory SH, Sagnimeni AJ, Wing EJ: Bacteria in the bloodstream are trapped in the liver and killed by immigrating neutrophils. J Immunol 157:2514–2520,1996
Rutledge BJ, Rayburn H, Rosenberg R, North RJ, Gladue RP, Crless CL, Rollins BJ: High level monocyte chemoattractant protein-1 expression in transgenic mice increases their susceptibility to intracellular pathogens. J Immunol 155:4838–4843,1995
Peters W, Scott HM, Chambers HF, Flynn JL, Charo IF, Ernst JD: Chemokine receptor 2 serves an early and essential role in resistance to Mycobacterium tuberculosis. Proc Natl Acad Sci U S A 98:7958–7963,2001
Kielian T, Barry B, Hickey WF: CXC chemokine receptor-2 ligands are required for neutrophil-mediated host defense in experimental brain abscesses. J Immunol 166:4634–4643,2001
Greenberger MJ, Strieter RM, Kunkel SL, Danforth JM, Laichalk LL, McGillicuddy DC, Standiford TJ: Neutralization of macrophage inflammatory protein-2 attenuates neutrophil recruitment and bacterial clearance in murine Klebsiella pneumonia. J Infect Dis 173:159–165,1996
Tauzon CU, Perez A, Kishiba T, Sheegren JN: Staphylococcus aureus among insulin-injecting diabetic patients. JAMA 231:1272,1975