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Ahnak-knockout mice show susceptibility to Bartonella henselae infection because of CD4+ T cell inactivation and decreased cytokine secretion
Eun Wha Choi1,2,*, Hee Woo Lee3, Jun Sik Lee4, Il Yong Kim5, Jae Hoon Shin5, Je Kyung Seong5,6
1Department of Veterinary Clinical Pathology,, College of Veterinary Medicine & Institute of Veterinary Science, Kangwon National University,
2Laboratory Animal Research Center, Samsung Biomedical Research Institute, Samsung Medical Center,
3Institute of Research and Development, Chaon Corp.,
4Department of Biology, Immunology Research Lab, College of Natural Sciences, Chosun University,
5Laboratory of Developmental Biology and Genomics, College of Veterinary Medicine, and Korea Mouse Phenotyping Center , Seoul National University,
6Interdiscplinary Program for Bioinformatics, Seoul National University
The present study evaluated the role of AHNAK in Bartonella henselae infection. Mice were intraperitoneally inoculated with 2 】 108 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-ャ (IFN-ャ)+ 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-ャ and IL-4 secretion in the splenocytes obtained from the B. henselae-infected wild-type mice, but did not increase IFN-ャ and IL-4 secretion in the splenocytes obtained from the B. henselae-infected Ahnak-KO mice. In contrast, IL-1メ, IL-1モ, IL-6, IL-10, RANTES, and tumor necrosis factor-メ 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-ャ and IL-4 secretion in the Ahnak-knockout mice suggests the impairment of Th1 and Th2 immunity in these mice.
Abstract, Accepted Manuscript(in press) [Submitted on December 20, 2018, Accepted on March 20, 2019]
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