Impairment of host resistance to Listeria monocytogenes infection in liver of db/db and ob/ob mice.
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.
Ikejima
Shin
S
Department of Bacteriology, Hirosaki University School of Medicine, Zaifu-cho 5, Hirosaki, Aomori 036-8562, Japan.
Sasaki
Sanae
S
Sashinami
Hiroshi
H
Mori
Fumiaki
F
Ogawa
Yoshiji
Y
Nakamura
Teruo
T
Abe
Yoshinao
Y
Wakabayashi
Koichi
K
Suda
Toshihiro
T
Nakane
Akio
A
D000818:Animals; D018932:Chemokine CCL2 / Q000235:genetics; D003114:Colony-Forming Units Assay; D016207:Cytokines / Q000235:genetics; D017931:DNA Primers; D004198:Disease Susceptibility; D007113:Immunity, Innate; D007249:Inflammation; D008089:Listeria monocytogenes; D008088:Listeriosis / Q000235:genetics*; D008099:Liver / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout; D008820:Mice, Obese; D012333:RNA, Messenger / Q000235:genetics; D011956:Receptors, Cell Surface / Q000172:deficiency* / Q000235:genetics; D054411:Receptors, Leptin; D020133:Reverse Transcriptase Polymerase Chain Reaction
C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D016207:Cytokines; D017931:DNA Primers; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin