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Overexpression of EspL inhibits autophagy and antigen presentation to promote the intracellular survival of Mycobacterium tuberculosis avirulent strains

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Title: Overexpression of EspL inhibits autophagy and antigen presentation to promote the intracellular survival of Mycobacterium tuberculosis avirulent strains
Authors: Luxia Cai, Yingying Lei, Tianyi Xie, Yiling Liu, Yutong Fan, Bing Yang, Shuang Dong, Gang Cao, Xi Chen
Source: Animal Diseases, Vol 4, Iss 1, Pp 1-13 (2024)
Publisher Information: BMC, 2024.
Publication Year: 2024
Collection: LCC:Veterinary medicine
LCC:Public aspects of medicine
Subject Terms: Mycobacterium tuberculosis, EspL, Pathogenicity, Autophagy, Antigen presentation, T-cell responses, Veterinary medicine, SF600-1100, Public aspects of medicine, RA1-1270
More Details: Abstract Mycobacterium tuberculosis (Mtb) employs multiple mechanisms, such as phagocytosis and autophagy, to evade innate immune clearance and establish infection. In the present study, we identified the ESX-1 secretion-associated protein EspL, which promotes Mtb survival by inhibiting phagosome maturation and autophagy initiation. EspL knockout decreased Mtb intracellular survival, while EspL overexpression increased bacterial survival by interfering with phagocytosis and autophagy. EspL interacts with ULK1 and promotes its phosphorylation at Ser757, leading to the inhibition of autophagy initiation. Additionally, overexpression of EspL reduced antigen presentation and T-cell responses both in vitro and in vivo. Our findings revealed that EspL interferes with autophagy and antigen presentation by suppressing ULK1 activation. These insights provide a novel understanding of Mtb pathogenicity.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 2731-0442
Relation: https://doaj.org/toc/2731-0442
DOI: 10.1186/s44149-024-00128-9
Access URL: https://doaj.org/article/f9d30747dfd94ecb8a6b2edf77328d43
Accession Number: edsdoj.f9d30747dfd94ecb8a6b2edf77328d43
Database: Directory of Open Access Journals
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  Data: Overexpression of EspL inhibits autophagy and antigen presentation to promote the intracellular survival of Mycobacterium tuberculosis avirulent strains
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  Data: <searchLink fieldCode="AR" term="%22Luxia+Cai%22">Luxia Cai</searchLink><br /><searchLink fieldCode="AR" term="%22Yingying+Lei%22">Yingying Lei</searchLink><br /><searchLink fieldCode="AR" term="%22Tianyi+Xie%22">Tianyi Xie</searchLink><br /><searchLink fieldCode="AR" term="%22Yiling+Liu%22">Yiling Liu</searchLink><br /><searchLink fieldCode="AR" term="%22Yutong+Fan%22">Yutong Fan</searchLink><br /><searchLink fieldCode="AR" term="%22Bing+Yang%22">Bing Yang</searchLink><br /><searchLink fieldCode="AR" term="%22Shuang+Dong%22">Shuang Dong</searchLink><br /><searchLink fieldCode="AR" term="%22Gang+Cao%22">Gang Cao</searchLink><br /><searchLink fieldCode="AR" term="%22Xi+Chen%22">Xi Chen</searchLink>
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  Data: Animal Diseases, Vol 4, Iss 1, Pp 1-13 (2024)
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  Data: BMC, 2024.
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  Data: 2024
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  Data: LCC:Veterinary medicine<br />LCC:Public aspects of medicine
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  Data: <searchLink fieldCode="DE" term="%22Mycobacterium+tuberculosis%22">Mycobacterium tuberculosis</searchLink><br /><searchLink fieldCode="DE" term="%22EspL%22">EspL</searchLink><br /><searchLink fieldCode="DE" term="%22Pathogenicity%22">Pathogenicity</searchLink><br /><searchLink fieldCode="DE" term="%22Autophagy%22">Autophagy</searchLink><br /><searchLink fieldCode="DE" term="%22Antigen+presentation%22">Antigen presentation</searchLink><br /><searchLink fieldCode="DE" term="%22T-cell+responses%22">T-cell responses</searchLink><br /><searchLink fieldCode="DE" term="%22Veterinary+medicine%22">Veterinary medicine</searchLink><br /><searchLink fieldCode="DE" term="%22SF600-1100%22">SF600-1100</searchLink><br /><searchLink fieldCode="DE" term="%22Public+aspects+of+medicine%22">Public aspects of medicine</searchLink><br /><searchLink fieldCode="DE" term="%22RA1-1270%22">RA1-1270</searchLink>
– Name: Abstract
  Label: Description
  Group: Ab
  Data: Abstract Mycobacterium tuberculosis (Mtb) employs multiple mechanisms, such as phagocytosis and autophagy, to evade innate immune clearance and establish infection. In the present study, we identified the ESX-1 secretion-associated protein EspL, which promotes Mtb survival by inhibiting phagosome maturation and autophagy initiation. EspL knockout decreased Mtb intracellular survival, while EspL overexpression increased bacterial survival by interfering with phagocytosis and autophagy. EspL interacts with ULK1 and promotes its phosphorylation at Ser757, leading to the inhibition of autophagy initiation. Additionally, overexpression of EspL reduced antigen presentation and T-cell responses both in vitro and in vivo. Our findings revealed that EspL interferes with autophagy and antigen presentation by suppressing ULK1 activation. These insights provide a novel understanding of Mtb pathogenicity.
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        Value: 10.1186/s44149-024-00128-9
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      – Text: English
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        PageCount: 13
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      – SubjectFull: Mycobacterium tuberculosis
        Type: general
      – SubjectFull: EspL
        Type: general
      – SubjectFull: Pathogenicity
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      – TitleFull: Overexpression of EspL inhibits autophagy and antigen presentation to promote the intracellular survival of Mycobacterium tuberculosis avirulent strains
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              Type: published
              Y: 2024
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