The Capsule of Porphyromonas gingivalis Leads to a Reduction in the Host Inflammatory Response, Evasion of Phagocytosis, and Increase in Virulence

Abstract

Periodontal disease is a chronic oral inflammatory disease that is triggered by bacteria such as Porphyromonas gingivalis. P. gingivalis strains exhibit great heterogeneity, with some strains being encapsulated while others are nonencapsulated. Although the encapsulated strains have been shown to be more virulent in a mouse abscess model, so far the role of the capsule in P. gingivalis interactions with host cells is not well understood and its role in virulence has not been defined. Here, we investigated the contribution of the capsule to triggering a host response following microbial infection, as well as its protective role following bacterial internalization by host phagocytic cells with subsequent killing, using the encapsulated P. gingivalis strain W50 and its isogenic nonencapsulated mutant, PgC. Our study shows significant time-dependent upregulation of the expression of various groups of genes in macrophages challenged with both the encapsulated and nonencapsulated P. gingivalis strains. However, cells infected with the nonencapsulated strain showed significantly higher upregulation of 9 and 29 genes at 1 h and 8 h postinfection, respectively, than cells infected with the encapsulated strain. Among the genes highly upregulated by the nonencapsulated PgC strain were ones coding for cytokines and chemokines. Maturation markers were induced at a 2-fold higher rate in dendritic cells challenged with the nonencapsulated strain for 4 h than in dendritic cells challenged with the encapsulated strain. The rates of phagocytosis of the nonencapsulated P. gingivalis strain by both macrophages and dendritic cells were 4.5-fold and 7-fold higher, respectively, than the rates of phagocytosis of the encapsulated strain. On the contrary, the survival of the nonencapsulated P. gingivalis strain was drastically reduced compared to the survival of the encapsulated strain. Finally, the encapsulated strain exhibited greater virulence in a mouse abscess model. Our results indicate that the P. gingivalis capsule plays an important role in aiding evasion of host immune system activation, promoting survival of the bacterium within host cells, and increasing virulence. As such, it is a major virulence determinant of P. gingivalis.

The nucleoid-associated protein HUβ affects global gene expression in Porphyromonas gingivalis

“…For many pathogenic bacteria, surface polysaccharides play a key role in immune modulation and evasion (Comstock & Kasper, 2006). It has recently been shown that the K-antigen capsule of P. gingivalis aids in immune evasion, promoting survival of the bacterium within host cells and increasing virulence (Singh et al, 2011). Previously, we have shown that expression of PG0121 affects synthesis of K-antigen capsule (AlbertiSegui et al, 2010).…”

Cellular Response Mechanisms in Porphyromonas gingivalis Infection

“…Also, depending on the type of lipid A expressed, P. gingivalis can act as both a TLR4 agonist and an antagonist and regulate the TLR4-dependent immune responses [10,18]. Realizing all the clever ways of escaping, it may not come as a surprise that P. gingivalis, as an additional function on the repertoire, also is resistant to oxidative killing by phagocytes and can survive phagocytosis by macrophages [26,30]. Furthermore, P. gingivalis is able to activate the coagulation cascade and the kallikrein/kinin cascade, thereby enhancing inflam mation [31][32][33].…”

“…Encapsulated strains are more virulent since they have been shown to be more invasive and more resistant to phagocytosis [25][26][27]. P. gingivalis also releases outer membrane vesicles, small cargos that are shed from the outer bacterial membrane that are loaded with LPS, gingipains and other proteases, fimbriae, and capsule (encapsulated strains).…”

Porphyromonas gingivalis infection in gestational diabetes mellitus and survival in tobacco smokers.

“…This minimal P. gingivalis genome is rich in genes performing critical physiological processes, particularly pyrimidine metabolism as well as lipopolysaccharide, peptidoglycan, and coenzyme A biosynthesis. Those genes that encode established virulence factors, such as gingipains [101], fimbriae [314], capsule [105], and RagB [315], are underrepresented in this overlapping gene set, probably because there is no immune or competing microbial challenge to be met. In other words, they are likely to be conditionally essential rather than inherently essential.…”

“…Six different serotypes of capsules have been identified depending on capsular polysaccharide Kantigens and their capacity to generate systemic IgG antibodies [104]. Bacterial encapsulation is positively correlated with increased resistance to phagocytosis [105]. In comparison to non-encapsulated strains, encapsulated P. gingivalis strains are shown to be highly invasive, causing spreading infection in a murine lesion model and more resistance to phagocytosis by PMN [106,107].…”