COPB1-knockdown induced type I interferon signaling activation inhibits Chlamydia psittaci intracellular proliferation.

IF 4 2区 生物学 Q2 MICROBIOLOGY Frontiers in Microbiology Pub Date : 2025-03-06 eCollection Date: 2025-01-01 DOI:10.3389/fmicb.2025.1566239
Nana Li, Huiying Yang, Shan Zhang, Yufei Jiang, Yinhui Lin, Xiaoxiao Chen, Yuchen Zhang, Yonghui Yu, Xuan Ouyang, Yujun Cui, Yajun Song, Jun Jiao
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Abstract

Objective: Chlamydia psittaci is a zoonotic pathogen that causes an acute disease known as psittacosis. To establish infection in host cells, Chlamydia manipulates the host cell's membrane trafficking pathways.

Methods: In this study, using fluorescently labeled C. psittaci and screening a human membrane trafficking small interfering RNA (siRNA) library, we identified 34 host proteins that influenced C. psittaci infection in HeLa cells.

Results: Among these, knockdown (KD) of two genes encoding subunits of the coatomer complex I (COPI) inhibited the pathogen's intracellular survival. Specifically, the knockdown of COPB1, a COPI subunit, significantly reduced the intracellular proliferation of C. psittaci. Mechanistically, we found that type I interferon negatively affected C. psittaci infection. Moreover, COPB1 KD disrupted the homeostasis of STING, preventing its retrieval from the Golgi back to the endoplasmic reticulum (ER), which in turn activated type I interferon signaling.

Conclusion: Together, our findings advance the understanding of the mechanisms underlying Chlamydia infection and offer potential avenues for the development of new anti-C. psittaci strategies.

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copb1敲低诱导I型干扰素信号激活抑制鹦鹉热衣原体细胞内增殖。
目的:鹦鹉热衣原体是一种人畜共患的病原体,会引起一种被称为鹦鹉热的急性疾病。为了在宿主细胞中建立感染,衣原体操纵宿主细胞的膜运输途径:在这项研究中,我们使用荧光标记的鹦鹉热衣原体并筛选了人类膜贩运小干扰 RNA(siRNA)文库,确定了 34 种影响鹦鹉热衣原体在 HeLa 细胞中感染的宿主蛋白:结果:其中,敲除(KD)两个编码衣壳复合体I(COPI)亚基的基因抑制了病原体在细胞内的存活。具体来说,敲除 COPB1(一种 COPI 亚基)能显著减少鹦鹉热杆菌在细胞内的增殖。从机理上讲,我们发现 I 型干扰素对猫疫病感染有负面影响。此外,COPB1 KD破坏了STING的平衡,阻止其从高尔基体检索回内质网(ER),进而激活了I型干扰素信号:总之,我们的研究结果加深了人们对衣原体感染机制的理解,并为开发新的抗鹦鹉热策略提供了潜在的途径。
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来源期刊
CiteScore
7.70
自引率
9.60%
发文量
4837
审稿时长
14 weeks
期刊介绍: Frontiers in Microbiology is a leading journal in its field, publishing rigorously peer-reviewed research across the entire spectrum of microbiology. Field Chief Editor Martin G. Klotz at Washington State University is supported by an outstanding Editorial Board of international researchers. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide.
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