Complement C3 deposition restricts the proliferation of internalized Staphylococcus aureus by promoting autophagy.

Autor:	Deng Y; National Key Laboratory of Veterinary Public Health, Animal Disease Diagnostic Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing, China.; College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, United States., Zhang Y; Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China., Wu T; Biotechnology Research Institute, Chinese Academy of Agricultural Sciences, Beijing, China., Niu K; National Key Laboratory of Veterinary Public Health, Animal Disease Diagnostic Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing, China., Jiao X; National Key Laboratory of Veterinary Public Health, Animal Disease Diagnostic Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing, China., Ma W; National Key Laboratory of Veterinary Public Health, Animal Disease Diagnostic Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing, China., Peng C; National Key Laboratory of Veterinary Public Health, Animal Disease Diagnostic Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing, China., Wu W; National Key Laboratory of Veterinary Public Health, Animal Disease Diagnostic Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing, China.
Jazyk:	angličtina
Zdroj:	Frontiers in cellular and infection microbiology [Front Cell Infect Microbiol] 2024 Sep 06; Vol. 14, pp. 1400068. Date of Electronic Publication: 2024 Sep 06 (Print Publication: 2024).
DOI:	10.3389/fcimb.2024.1400068
Abstrakt:	Complement C3 (C3) is usually deposited spontaneously on the surfaces of invading bacteria prior to internalization, but the impact of C3 coating on cellular responses is largely unknown. Staphylococcus aureus ( S. aureus ) is a facultative intracellular pathogen that subverts autophagy and replicates in both phagocytic and nonphagocytic cells. In the present study, we deposited C3 components on the surface of S. aureus by complement opsonization before cell infection and confirmed that C3-coatings remained on the surface of the bacteria after they have invaded the cells, suggesting S. aureus cannot escape or degrade C3 labeling. We found that the C3 deposition on S. aureus notably enhanced cellular autophagic responses, and distinguished these responses as xenophagy, in contrast to LC3-associated phagocytosis (LAP). Furthermore, this upregulation was due to the recruitment of and direct interaction with autophagy-related 16-like 1 (ATG16L1), thereby resulting in autophagy-dependent resistance to bacterial growth within cells. Interestingly, this autophagic effect occurred only after C3 activation by enzymatic cleavage because full-length C3 without cleavage of the complement cascade reaction, although capable of binding to ATG16L1, failed to promote autophagy. These findings demonstrate the biological function of intracellular C3 upon bacterial infection in enhancing autophagy against internalized S. aureus . Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2024 Deng, Zhang, Wu, Niu, Jiao, Ma, Peng and Wu.)
Databáze:	MEDLINE
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