Macrophage TRIM21 lactylation exacerbates infection-induced orchitis through enhancing STAT1-mediated CXCL9 and CXCL10 production.

ABSTRACT:

Introduction

Infection-induced orchitis, a leading cause of acquired male infertility affecting 8%-12% of couples globally, is driven by unresolved inflammatory responses following bacterial infection.

Methods

We employed uropathogenic Escherichia coli (UPEC)- and lipopolysaccharide (LPS)-induced orchitis models to define the mechanisms underlying testicular inflammation. We interrogated the cellular sources of CXCL9/CXCL10 and assessed macrophage-driven inflammatory cell recruitment and spermatogenic disruption. Mechanistic studies were focused on lysine lactylation, STAT1 protein stability, ubiquitin-proteasome-mediated degradation, and the role of the E3 ubiquitin ligase TRIM21.

Results

We demonstrate that macrophages are the predominant source of CXCL9 and

SUBMITTER: Tang W 

PROVIDER: S-EPMC12847007 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature