Abstract

Porphyromonas gingivalis (P. gingivalis) is a keystone pathogen in periodontitis. Our previous study indicated that periodontitis induced by P. gingivalis increased the percentage of CD19+ B cells, but decreased the ratio of IL-10 producing regulatory B cells (B10) in collagen-induced arthritis (CIA) mice. It's still unclear which virulence factors of P. gingivalis are involved in these processes. Here, we compared the effects of different components of P. gingivalis on the biogenesis of B10 cells, and found that the decreased proportion of B10 cells was mainly resulted from the undenatured proteins other than the DNA, RNA or LPS of P. gingivalis. As gingipains are enzymes and virulence factors which play vital role in the progression in periodontitis through affecting innate and adaptive immune system, we then compared the influence of the wild-type (WT) strain of P. gingivalis (ATCC 33277) and its isogenic gingipain-null mutant (∆K∆RAB) on differentiation of splenic B cells into B10 cells. Interestingly, compared to WT strain, ∆K∆RAB treatment increased the frequency of B10 cells as well as expression of IL-6 in B cells. Furthermore, the acute peritonitis, an ideal model for quick evaluation of immune effects of agents, induced by ∆K∆RAB showed higher IL-6 production and proportion of B10 cells compared with WT. Finally, we performed transcriptomic analysis to better understand the effects and possible mechanism of gingipains on B cells. Compared with WT, ∆K∆RAB upregulated the PI3K-Akt pathway of B cells which is important for IL-10 production and B10 cell biogenesis, and more activated Jak-STAT pathway which is a classical signaling pathway mediated by IL-6. Cumulatively, this study preliminarily revealed that gingipains of P. gingivalis are vital virulence factors downregulating B10 cells and altering immune responses. This article is protected by copyright. All rights reserved.