Variants of Porphyromonas gingivalis lipopolysaccharide alter lipidation of autophagic protein, microtubule‐associated protein 1 light chain 3, LC3

Abstract

Porphyromonas gingivalis often subverts host cell autophagic processes for its own survival. Our previous studies document the association of the cargo sorting protein, melanoregulin (MREG), with its binding partner, the autophagic protein, microtubule-associated protein 1 light chain 3 (LC3) in macrophages incubated with P. gingivalis (strain 33277). Differences in the lipid A moiety of lipopolysaccharide (LPS) affect the virulence of P. gingivalis; penta-acylated LPS is a weak Toll-like receptor 4 agonist compared with Escherichia coli LPS, whereas tetra-acylated LPS acts as an LPS antagonist. To determine how P. gingivalis LPS affects autophagy we assessed LC3-dependent and MREG-dependent processes in green fluorescent protein (GFP)-LC3-expressing Saos-2 cells. LPS stimulated the formation of very large LC3-positive vacuoles and MREG puncta. This LPS -mediated LC3 lipidation decreased in the presence of LPS . When Saos-2 cells were incubated with P. gingivalis the bacteria internalized but did not traffic to GFP-LC3-positive structures. Nevertheless, increases in LC3 lipidation and MREG puncta were observed. Collectively, these results suggest that P. gingivalis internalization is not necessary for LC3 lipidation. Primary human gingival epithelial cells isolated from patients with periodontitis showed both LC3II and MREG puncta whereas cells from disease-free individuals exhibited little co-localization of these two proteins. These results suggest that the prevalence of a particular LPS moiety may modulate the degradative capacity of host cells, so influencing bacterial survival.

The Role of Reactive Oxygen Species and Autophagy in Periodontitis and Their Potential Linkage

“…Taken together, these results strongly suggest that the induction of autophagy can facilitate specific periodontal bacterial survival by replication within an autophagosome-like compartment. However, no LC3 lipidation was found when cells were infected with A. actinomycetemcomitans (Blasi et al, 2016), suggesting that the activity of cellular autophagy in response to infection is associated with periodontal bacterial species.…”

“…The results showed increased LC3 expression and autophagosome production in inflammatory PDL tissues (An et al, 2016). In addition, co-localization of LC3 and melanoregulin (MREG) was found in gingival epithelial cells isolated from severe periodontal disease-affected individuals, while this effect was absent in cells from healthy or moderately affected individuals (Blasi et al, 2016). As multiple studies have proposed that autophagy may antagonize apoptosis, these results suggest a potential protective role of autophagy in periodontal tissues.…”

Importance of heterogeneity in Porhyromonas gingivalis lipopolysaccharide lipid A in tissue specific inflammatory signalling

“…In a study by Blasi et al [54], variants of P. gingivalis LPS altered lipidation of autophagy protein, i.e. microtubule-associated protein 1 light chain 3 (LC3).…”

Differential Regulation of Mas-Related G Protein-Coupled Receptor X2-Mediated Mast Cell Degranulation by Antimicrobial Host Defense Peptides and Porphyromonas gingivalis Lipopolysaccharide

“…PgLPS 1690 stimulates autophagy in Saos-2 osteosarcoma cells, and this effect is reversed by PgLPS 1435/1449 (74). Furthermore, autophagy is critical for IgE-dependent mast cell degranulation (75).…”