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<p><i>Brucella abortus</i>, an intracellular bacterium, employs intricate mechanisms to manipulate host signaling for persistence. This study investigates the role of STAT3 palmitoylation in <i>B. abortus</i>-infected macrophages. We demonstrate that <i>B. abortus</i> 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 <i>B. abortus</i> 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 <i>B. abortus</i> infection, linking lipid modification to STAT3 activation, inflammation, apoptosis, and bacterial persistence.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月5日

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  • Xiaofeng Liu,
  • Juntong Yu,
  • Yanjie Chen,
  • Haoran Liu,
  • Ning Liu,
  • Qisheng Peng

摘要

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.