期刊
JOURNAL OF EXTRACELLULAR VESICLES
卷 10, 期 6, 页码 -出版社
WILEY
DOI: 10.1002/jev2.12080
关键词
autophagy; bacterial membrane vesicles; bacterial pathogenesis; DNA; innate immunity; NOD2; peptidoglycan; RNA; Staphylococcus aureus; TLRs
类别
资金
- Australian Research Council [DP190101655]
- National Health and Medical Research Council [1107800]
- La Trobe University RFA Understanding Diseases Grant
- veski Inspiring Women Fellowship
- LIMS Bioimaging Facility (La Trobe University)
- National Health and Medical Research Council of Australia [1107800] Funding Source: NHMRC
Gram-positive bacteria produce membrane vesicles (MVs) containing microbe-associated molecular patterns (MAMPs) such as proteins, nucleic acids, and peptidoglycan, which can activate pattern recognition receptors (PRRs) in host epithelial cells and promote cytokine and chemokine release. Additionally, MVs can be degraded intracellularly through autophagy, enhancing our understanding of their immunostimulatory roles and fate within the host.
Gram-positive bacteria ubiquitously produce membrane vesicles (MVs), and although they contribute to biological functions, our knowledge regarding their composition and immunogenicity remains limited. Here we examine the morphology, contents and immunostimulatory functions of MVs produced by three Staphylococcus aureus strains; a methicillin resistant clinical isolate, a methicillin sensitive clinical isolate and a laboratory-adapted strain. We observed differences in the number and morphology of MVs produced by each strain and showed that they contain microbe-associated molecular patterns (MAMPs) including protein, nucleic acids and peptidoglycan. Analysis of MV-derived RNA indicated the presence of small RNA (sRNA). Furthermore, we detected variability in the amount and composition of protein, nucleic acid and peptidoglycan cargo carried by MVs from each S. aureus strain. S. aureus MVs activated Toll-like receptor (TLR) 2, 7, 8, 9 and nucleotide-binding oligomerization domain containing protein 2 (NOD2) signalling and promoted cytokine and chemokine release by epithelial cells, thus identifying that MV-associated MAMPs including DNA, RNA and peptidoglycan are detected by pattern recognition receptors (PRRs). Moreover, S. aureus MVs induced the formation of and colocalized with autophagosomes in epithelial cells, while inhibition of lysosomal acidification using bafilomycin A1 resulted in accumulation of autophagosomal puncta that colocalized with MVs, revealing the ability of the host to degrade MVs via autophagy. This study reveals the ability of DNA, RNA and peptidoglycan associated with MVs to activate PRRs in host epithelial cells, and their intracellular degradation via autophagy. These findings advance our understanding of the immunostimulatory roles of Gram-positive bacterial MVs in mediating pathogenesis, and their intracellular fate within the host.
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