Impairment of Host Resistance to Listeria monocytogenes Infection in Liver of db/db and ob/ob Mice

Institute of Brain Science, Hirosaki University, Khirosaki, Aomori, Japan
Diabetes (Impact Factor: 8.1). 02/2005; 54(1):182-9. DOI: 10.2337/diabetes.54.1.182
Source: PubMed


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.

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    • "In these studies, greater mortality in the ob/ob mouse was associated with impaired pulmonary bacterial clearance and attenuated alveolar macrophage and neutrophil phagocytosis and killing of bacteria, and the elaboration of reactive oxygen intermediates [22]. In addition, many other reports have demonstrated that ob/ob mice exhibit host defense defects in response to several other bacterial, mycobacterial, amoeba, and fungal infections [23]–[28]. However, leptin deficiency disables host defense, in the absence of obesity, and has been demonstrated to restore antimicrobial functions in the presence of obesity in ob/ob mice [21], [29]. "
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    PLoS ONE 09/2014; 9(9):e106420. DOI:10.1371/journal.pone.0106420 · 3.23 Impact Factor
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    • "Our data provide an explanation for recent findings linking impaired macrophage response and/or activity to various co-morbidities associated with diabetes. For example, it was reported that diabetic liver is more susceptible to Listeria monocytogenes infection [28]. This phenomenon was correlated with reduced CCL2 (MCP-1) expression in db/db liver, which suggests that inadequate macrophage response, due to CCL2 insufficiency, may be to blame for enhanced susceptibility to infection in that environment. "
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    PLoS ONE 03/2014; 9(3):e91574. DOI:10.1371/journal.pone.0091574 · 3.23 Impact Factor
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    • "This defect in the immune system is translated in diabetic patients to an enhanced susceptibility to infections, especially from gram negative bacteria [39], [40]. A similar defect in bacterial clearance has been demonstrated in old leptin receptor deficient db/db mice that indeed show weakened bacterial clearance of gram negative bacterial strains compared to heterozygote littermates [39], [40]. Moreover, a decline in LPS responsiveness in peritoneal macrophages from db/db mice with characteristics relevant to developed T2D has previously been reported [41]. "
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