Immune response of macrophages induced by Porphyromonas gingivalis requires HmuY protein

Abstract

The main etiologic agent and a key pathogen responsible for initiation and progression of chronic periodontitis is Porphyromonas gingivalis. We examined the role of P. gingivalis, with particular interest to HmuY protein, in expression of genes involved in Toll-like receptor (TLR)-induced signaling pathways using cell-based infection model. U937 and THP-1 cells differentiated toward macrophages by PMA treatment responded to P. gingivalis-caused infection in slightly different gene expression pattern, mainly by higher expression of genes encoding NF-κB, TLR7, TLR2, TLR8, pro-inflammatory cytokines (IL-1β, IL-6, TNFα), anti-inflammatory cytokine (IL-10), and chemokines (CCL3L1, CCL4, CXCL10, CXCL11, PTX3). P. gingivalis lacking functional hmuY gene stimulates immune response of macrophages, albeit in a different manner as compared with the wild-type strain, mainly by lower expression of genes encoding NF-κB, IL-1β, IL-10, CD80, PTX3, and CCL31L. The purified HmuY protein alone induced expression of genes encoding IL-6, IL-10, TNFα, CCL3L1, and CCL4. We conclude that macrophages respond to P. gingivalis infection mostly by TLR7-induced pathway(s). Moreover, P. gingivalis HmuY is one of important virulence factors, which allows P. gingivalis for in vivo growth in the heme-limited host environment, resulting in efficient immune response of macrophages.

Keywords: Cytokine; HmuY; Macrophage; Periodontitis; Porphyromonas gingivalis; Toll-like receptor.