Work

Brucella abortus infection exploits ZDHHC3-mediated STAT3 palmitoylation to regulate host responses and promote persistence

Year: 2026

Type: article

Abstract: Brucella abortus, an intracellular bacterium, employs intricate mechanisms to manipulate host signaling for persistence. This study investigates the role of STAT3 palmitoylation in B. abortus-infected macrophages. We demonstrate that B. abortus infection induces STAT3 palmitoylation, which is critical for its membrane recruitment. Among zinc finger DHHC-type palmitoyl acyltransferases (ZDHHC) family members, ZDHHC3 specifically mediates STAT3 palmitoylation in infected macrophages. ZDHHC3-induced STAT3 palmitoylation promotes STAT3 phosphorylation at Y705, independently of IL-6. Functionally, ZDHHC3 suppresses pro-inflammatory cytokines (IL-1β, TNF-α) and nitric oxide (NO) production, while increasing anti-inflammatory IL-10, thereby enhancing intracellular B. abortus survival. In vivo, ZDHHC3 mRNA is upregulated in splenic macrophages during infection, and 2-bromopalmitate (2BP) treatment reduces bacterial burden in mice, associated with elevated TNF-α and IFN-γ. Additionally, ZDHHC3 inhibits macrophage apoptosis (via regulating Bax and Bcl-2), limiting bacterial egress from apoptotic cells. These findings identify ZDHHC3-mediated STAT3 palmitoylation as one of the key regulatory mechanism in B. abortus infection, linking lipid modification to STAT3 activation, inflammation, apoptosis, and bacterial persistence.

Source: Veterinary Research

DOI: 10.1186/s13567-025-01681-y

Authors: Xiaofeng Liu, Juntong Yu, Yanjie Chen, Haoran Liu, Ning Liu, Qisheng Peng

Institutions: Jilin University, Jilin Province Tumor Hospital, Second Affiliated Hospital of Jilin University

Language: English

Topic: Brucella: diagnosis, epidemiology, treatment

Subfield: Small Animals

Field: Veterinary

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,390