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Candida albicans 감염에 의한 선천성 면역 방어에서 CCR5 및 IL-33에 의해 형성된 신장 면역 네트워크의 역할

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Abstract
Candida albicans (C. albicans) is a crucial pathogen that cause a serious health problem, inducing high mortality rates in immunocompromised patients. Understanding the innate immune pathway that controls antifungal defense in kidney, a major target organs, remains to be clarified. In this thesis, using in vitro and in vivo experiments systems, I demonstrated that C-C chemokine receptor type 5 (CCR5) and Interleukin- 33 (IL-33) played a critical role in innate defense to systemic C.albicans infection.
In the first part of study, I showed that using CCR5-deficient (Ccr5-/-) mice, CCR5 contributes to an effective defense mechanism against systemic C. albicans infection. CCR5 was required for recruitment of NK cells to the kidney after systemic C. albicans infection. In Ccr5-/- mice, there were lower levels of GM-CSF in the kidney, which resulted in impaired neutrophils’ fungal clearance. Taken together with previous results showing that C. albicans activated the dendritic cell (DC)  IL-23  NK cell  GM-CSF  neutrophil defense axis, the results obtained form this study indicates that CCR5 play a main role in recruiting NK cells to the kdiney during systemic C. albicans infection.
In the second part, I investigated in vivo function of endogenous Il-33 in systemic C. albicans infection using Il33-/- mice. IL-33 initiated an innate defense mechanism by co-stimulating DCs to produce IL-23 after systemic C. albicans infection. As a result, NK cells could not secrete amounts of GM-CSF suffieint to stimulate nuetrophils to phagocytize proliferating C. albicans. The susceptibility of Il33-/- mice was also associated with increased levels of IL-10 and neutralization of IL-10 resulted in enhanced fungal clearance in these mice. However, depletion of IL-10 overrided the effect of IL-33 on fungal clearance. There were abnormally differentiationed MHCII+F4/80+ macrophages in Il10-/- mouse kidnneys, which were superior to MHCII-F4/80+ macrophage that were presnt in WT mouse kidneys, in killing of extracellular hyphal form of C. albicans.
Taken together, our results identify IL-33 and CCR5 as critical regulator creating an innate immune network cirtical for defense during systemic C. albicans infection.
Author(s)
웬 누 젠 나
Issued Date
2022
Awarded Date
2022-02
Type
dissertation
URI
https://oak.ulsan.ac.kr/handle/2021.oak/9838
http://ulsan.dcollection.net/common/orgView/200000595336
Alternative Author(s)
Nguyen Nu Zen Na
Affiliation
울산대학교
Department
일반대학원 생명과학과
Advisor
권병석
Degree
Doctor
Publisher
울산대학교 일반대학원 생명과학과
Language
eng
Rights
울산대학교 논문은 저작권에 의해 보호 받습니다.
Appears in Collections:
Life Science > 2. Theses (Ph.D)
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