[Bacteria killing by macrophages via NF-IL6 gene dependent mechanism: the susceptibility to Mycobacterium leprae in NF-IL6 knockout mice].
Transcription factor, NF-IL6 recognizes the same nucleotide sequences as C/EBP, and it is predominantly expressed in macrophages. Tanaka et al. reported that NF-IL6 knockout mice are highly susceptible to Listeria monocytogenes and Salmonella typhimurium due to impairment of bacteria killing by activated macrophages. We have tried to see the susceptibility for Mycobacterium leprae infection with intraperitoneal(i.p.) or both hind foot pad (BHF) in the NF-IL6 knockout mice with wild control mice. Although we examined the cytokine genes expression and induction of such as IL-1 alpha, IL-6, IL-12, IL-18/IGIF, NO2. and TNF alpha in the peritoneal macrophages on 1 month after inoculation, also IL-2 and IL-10 by splenocytes on 1 and 8 months after infection. Following the inoculation of M. leprae with i.p. or BHF, the mice were sacrificed from 1 to 12 months after inoculation in order to confirm the multiplication and the dissemination of the infection. Many leprosy bacilli was found in the peritoneal macrophages of NF-IL6 knockout mice on 1 month after inoculation while that of the wild control mice was showing disappear. In the case of the intraperitoneal infection, NF-IL6 knockout mice shows predominantly multiplication of M. leprae on the abdemino-organs such as omentum and also scrotum with male. Although NF-IL6 knockout mice with BHF inoculation did not show any swelling at the site of inoculated foot, however the foot pad on 12 month after inoculation was processed for Fite-Faraco's stain and microscopy shows many leprosy bacilli in the intermuscular layer or around the blood vessels/sciatic nerve in the subcutaneous tissue and then the multiplication extended to the toes. Besides the induction of cytokines such as IL-1 alpha, TNF alpha and IL-12 production were observed stronger in culture supernatant of peritoneal macrophages of NF-IL6 knockout mice than that of the wild control mice. IL-2 production was also observed strong in culture supernatant in splenocytes of NF-IL6 knockout mice while that of IL-10 production never induced at anytime. This is doubtless the results of impairment of bacteria killing by macrophages via NF-IL6 gene dependent mechanism not to antigen specific immune system.
Yogi
Y
Y
Leprosy Research Center, National Institute of Infectious Diseases.
Endoh
M
M
Tanaka
T
T
Akira
S
S
Okamura
H
H
Nomaguchi
H
H
D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins; D016207:Cytokines / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D007918:Leprosy / Q000235:genetics*; D017737:Macrophages, Peritoneal / Q000276:immunology* / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009166:Mycobacterium leprae; D009687:Nuclear Proteins / Q000235:genetics*; D010587:Phagocytosis / Q000235:genetics*
D022762:CCAAT-Enhancer-Binding Proteins; D016207:Cytokines; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins