# Macrophage activation and invasion by P. gingivalis is modulated by PPAD and accessory fimbriae subunits

## TL;DR

This study shows how P. gingivalis uses PPAD-modified fimbriae to manipulate macrophages, promoting inflammation and evading immune defenses.

## Contribution

The study reveals a novel role of PPAD-modified accessory fimbriae in immune evasion by P. gingivalis through macrophage manipulation.

## Key findings

- PPAD-modified fimbriae increase PGE2-related gene expression and cytokine secretion in macrophages.
- PPAD-modified accessory fimbriae protect P. gingivalis from macrophage killing.
- These fimbriae upregulate genes linked to viral infections and T cell interactions.

## Abstract

Porphyromonas gingivalis is a master manipulator of host immune responses in the periodontium. Peptidyl arginine deiminase (PPAD), a recently identified virulence factor of P. gingivalis, responsible for citrullination of both host- and bacterium-derived proteins and peptides, also plays a key role in hijacking immune responses. While PPAD's modification of fimbrial subunits (FimCDE) affects TLR2 signalling in fibroblasts, its effects on immune cells remain unclear.

Human monocyte-derived macrophages (MDMs) were stimulated with wild-type or mutant P. gingivalis strains and isolated fimbriae. Inflammatory responses were assessed by measuring cytokine expression and secretion, transcriptional changes using RNA-seq and Pi3K/Akt pathway activation, as well as bacterial invasion through flow cytometry, fluorescent microscopy, and intracellular survival assays.

PPAD-modified fimbriae stimulated MDM pro-inflammatory responses, such as PGE2-related gene expression and cytokine secretion, while fimbriae from accessory subunit mutants failed to induce inflammation. PPAD modification of accessory fimbrial subunits was found to protect P. gingivalis from macrophage killing. PPAD and accessory fimbriae subunits participated in complex immune evasion strategies, upregulating genes linked to viral infections or T cell interactions.

These findings highlight the importance of protein citrullination in TLR2-related signaling and offer insight into how P. gingivalis evades host immune responses.

PPAD-modified fimbriae enhanced expression of enzymes in the PGE2 synthesis pathway and secretion of cytokines interleukin (IL)-6 and IL-8 from human monocyte-derived macrophage (MDM).PPAD-modified accessory fimbrial subunits protected P. gingivalis from killing by macrophages.PPAD and accessory fimbriae subunits are important in complex immune evasion strategies, upregulating genes associated with viral infections or interactions with T cells.

PPAD-modified fimbriae enhanced expression of enzymes in the PGE2 synthesis pathway and secretion of cytokines interleukin (IL)-6 and IL-8 from human monocyte-derived macrophage (MDM).

PPAD-modified accessory fimbrial subunits protected P. gingivalis from killing by macrophages.

PPAD and accessory fimbriae subunits are important in complex immune evasion strategies, upregulating genes associated with viral infections or interactions with T cells.