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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Ahnak-knockout mice show susceptibility to Bartonella henselae infection because of CD4+ T cell inactivation and decreased cytokine secretion

  • Choi, Eun Wha (Department of Veterinary Clinical Pathology, College of Veterinary Medicine & Institute of Veterinary Science, Kangwon National University) ;
  • Lee, Hee Woo (Institute of Research and Development, Chaon Corp.) ;
  • Lee, Jun Sik (Department of Biology, Immunology Research Lab., College of Natural Sciences, Chosun University) ;
  • Kim, Il Yong (Laboratory of Developmental Biology and Genomics, BK21 Plus Program for Advanced Veterinary Science, Research Institute for Veterinary Science, College of Veterinary Medicine, and Korea Mouse Phenotyping Center, Seoul National University) ;
  • Shin, Jae Hoon (Laboratory of Developmental Biology and Genomics, BK21 Plus Program for Advanced Veterinary Science, Research Institute for Veterinary Science, College of Veterinary Medicine, and Korea Mouse Phenotyping Center, Seoul National University) ;
  • Seong, Je Kyung (Laboratory of Developmental Biology and Genomics, BK21 Plus Program for Advanced Veterinary Science, Research Institute for Veterinary Science, College of Veterinary Medicine, and Korea Mouse Phenotyping Center, Seoul National University)
  • Received : 2018.12.20
  • Accepted : 2019.03.20
  • Published : 2019.04.30
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Abstract

The present study evaluated the role of AHNAK in Bartonella henselae infection. Mice were intraperitoneally inoculated with $2{\times}10^8$ colony-forming units of B. henselae Houston-1 on day 0 and subsequently on day 10. Blood and tissue samples of the mice were collected 8 days after the final B. henselae injection. B. henselae infection in the liver of Ahnak-knockout and wild-type mice was confirmed by performing polymerase chain reaction, with Bartonella adhesion A as a marker. The proportion of B. henselae-infected cells increased in the liver of the Ahnak-knockout mice. Granulomatous lesions, inflammatory cytokine levels, and liver enzyme levels were also higher in the liver of the Ahnak-knockout mice than in the liver of the wild-type mice, indicating that Ahnak deletion accelerated B. henselae infection. The proportion of CD4+interferon-${\gamma}$ ($IFN-{\gamma}^+$) and $CD4^+$ interleukin $(IL)-4^+$ cells was significantly lower in the B. henselae-infected Ahnak-knockout mice than in the B. henselae-infected wild-type mice. In vitro stimulation with B. henselae significantly increased $IFN-{\gamma}$ and IL-4 secretion in the splenocytes obtained from the B. henselae-infected wild-type mice, but did not increase $IFN-{\gamma}$ and IL-4 secretion in the splenocytes obtained from the B. henselae-infected Ahnak-KO mice. In contrast, $IL-1{\alpha}$, $IL-1{\beta}$, IL-6, IL-10, RANTES, and tumor necrosis $factor-{\alpha}$ secretion was significantly elevated in the splenocytes obtained from both B. henselae-infected wild-type and Ahnak-knockout mice. These results indicate that Ahnak deletion promotes B. henselae infection. Impaired $IFN-{\gamma}$ and IL-4 secretion in the Ahnak-knockout mice suggests the impairment of Th1 and Th2 immunity in these mice.

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References

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