Hos, Nina Judith, Fischer, Julia, Hos, Deniz, Hejazi, Zahra, Calabrese, Chiara, Ganesan, Raja, Murthy, Ambika M., V, Rybniker, Jan, Kumar, Sharad ORCID: 0000-0001-7126-9814, Kronke, Martin and Robinson, Nirmal ORCID: 0000-0002-7361-9491 (2020). TRIM21 Is Targeted for Chaperone-Mediated Autophagy during Salmonella Typhimurium Infection. J. Immunol., 205 (9). S. 2456 - 2471. BETHESDA: AMER ASSOC IMMUNOLOGISTS. ISSN 1550-6606
Full text not available from this repository.Abstract
Salmonella enterica serovar Typhimurium (S. Typhimurium) is a Gram-negative bacterium that induces cell death of macrophages as a key virulence strategy. We have previously demonstrated that the induction of macrophage death is dependent on the host's type I IFN (IFN-I) response. IFN-I signaling has been shown to induce tripartite motif (TRIM) 21, an E3 ubiquitin ligase with critical functions in autoimmune disease and antiviral immunity. However, the importance and regulation of TRIM21 during bacterial infection remains poorly understood. In this study, we investigated the role of TRIM21 upon S. Typhimurium infection of murine bone marrow-derived macrophages. Although Trim2/ expression was induced in an IFN-I-dependent manner, we found that TRIM21 levels were mainly regulated posttranscriptionally. Following TLR4 activation, TRIM21 was transiently degraded via the lysosomal pathway by chaperone-mediated autophagy (CMA). However, S. Typhimurium-induced mTORC2 signaling led to phosphorylation of Akt at 5473, which subsequently impaired TRIM21 degradation by attenuating CMA. Elevated TRIM21 levels promoted macrophage death associated with reduced transcription of NF erythroid 2-related factor 2 (NRF2)-dependent antioxidative genes. Collectively, our results identify IFN-I-inducible TRIM21 as a negative regulator of innate immune responses to S. Typhimurium and a previously unrecognized substrate of CMA. To our knowledge, this is the first study reporting that a member of the TRIM family is degraded by the lysosomal pathway.
Item Type: | Journal Article | ||||||||||||||||||||||||||||||||||||||||||||||||
Creators: |
|
||||||||||||||||||||||||||||||||||||||||||||||||
URN: | urn:nbn:de:hbz:38-313826 | ||||||||||||||||||||||||||||||||||||||||||||||||
DOI: | 10.4049/jimmunol.2000048 | ||||||||||||||||||||||||||||||||||||||||||||||||
Journal or Publication Title: | J. Immunol. | ||||||||||||||||||||||||||||||||||||||||||||||||
Volume: | 205 | ||||||||||||||||||||||||||||||||||||||||||||||||
Number: | 9 | ||||||||||||||||||||||||||||||||||||||||||||||||
Page Range: | S. 2456 - 2471 | ||||||||||||||||||||||||||||||||||||||||||||||||
Date: | 2020 | ||||||||||||||||||||||||||||||||||||||||||||||||
Publisher: | AMER ASSOC IMMUNOLOGISTS | ||||||||||||||||||||||||||||||||||||||||||||||||
Place of Publication: | BETHESDA | ||||||||||||||||||||||||||||||||||||||||||||||||
ISSN: | 1550-6606 | ||||||||||||||||||||||||||||||||||||||||||||||||
Language: | English | ||||||||||||||||||||||||||||||||||||||||||||||||
Faculty: | Unspecified | ||||||||||||||||||||||||||||||||||||||||||||||||
Divisions: | Unspecified | ||||||||||||||||||||||||||||||||||||||||||||||||
Subjects: | no entry | ||||||||||||||||||||||||||||||||||||||||||||||||
Uncontrolled Keywords: |
|
||||||||||||||||||||||||||||||||||||||||||||||||
URI: | http://kups.ub.uni-koeln.de/id/eprint/31382 |
Downloads
Downloads per month over past year
Altmetric
Export
Actions (login required)
View Item |