LPS-defective Porphyromonas Gingivalis Mutant Down-regulates the Dendritic Cell-induced Immune Response

Objectives: Periodontitis is a chronic immuno-inflammatory disease elicited by a dysbiotic subgingival biofilm, and characterized by the progressive destruction of teeth-supporting tissues. Porphyromonas gingivalis is a Gram-negative anaerobic bacterium considered as a keystone in the aetiology of periodontitis. Among its virulence factors, lipopolysaccharide (LPS) plays a central role in the pathogenesis of periodontitis, and particularly the O-polysaccharide (O-PS) is the immuno-dominant fraction of P. gingivalis LPS. Identification and characterization of the O-PS locus of P. gingivalis allowed for the generation of a isogenic LPS−deficient mutant (ΔPG1051). Thus, this study was aimed to compare the immune response triggered by human dendritic cells (hDCs) when are stimulated with this W50 strain-based isogenic capsular-defective P. gingivalis mutant or the W50 wild-type strain.
Methods: Monocyte-derived hDCs were stimulated with the P. gingivalis W50 wild-type strain or ΔPG1051 mutant of P. gingivalis for 2 days. Non-infected hDCs and hDCs stimulated with the LPS-complemented cΔPG1051 strain were used as control. The mRNA expression levels for Th1-related cytokines (IL-1β, IL-12, TNF-α, and IFN-γ) and Th17-related cytokines (IL-6, IL-21, and IL-23) were quantified by qPCR.
Results: P. gingivalis ΔPG1051 mutant strain triggered less expression levels of Th1 and Th17-related cytokines in stimulated hDCs than the W50 wild-type. When hDCs were induced with the complemented cΔPG1051 strain, cytokine levels were similar than those detected upon W50 wild-type-stimulation.
Conclusions: These results demonstrate that ΔPG1051 mutant strain down-regulates the immune response against P. gingivalis in hDCs. Thus, further demonstrating that LPS is a hallmark of virulence heterogeneity of P. gingivalis.