Extracellular Prdx1 mediates bacterial infection and inflammatory bone diseases.

AIM: We aimed to determine the role of extracellular peroxiredoxin 1 (Prdx1) in the pathogenesis of bacterial infections and inflammatory bone disease.

MATERIALS AND

METHODS

We first investigated the role of Prdx1 using knockout mice. Next, we determined the role of extracellular Prdx1 in bacterial infections by using a neutralizing antibody against Prdx1. We finally investigated whether blockade of extracellular Prdx1 affected high- or low-grade inflammatory bone diseases using calvarial osteolysis, collagen-induced arthritis (CIA), and microgravity-induced bone loss in mouse models.

KEY FINDINGS: The lack of Prdx1 increased susceptibility to infections by Listeria monocytogenes or Escherichia coli. Prdx1 is released into the serum upon E. coli infection, and blockade of extracellular Prdx1 confers significant protection against bacterial infections. Our data suggested that circulating Prdx1 is increased by the development of osteolytic disease, and that blockade of extracellular Prdx1 exerts therapeutic effects against high- and low-grade inflammatory bone loss. In addition, the release of Prdx1 under inflammatory osteolytic conditions partly depends on non-canonical TIR-domain-containing adapter-inducing interferon-β (TRIF)-caspase-11-gasdemin D (GSDMD) inflammasome pathways.

SIGNIFICANCE: Extracellular Prdx1 is involved in the development of bacterial infections and inflammatory bone disease. Thus, extracellular Prdx1 may represent a novel therapeutic target for bacterial infections or inflammatory osteolytic diseases.