Distinct STING-IRF3 activation determines IL-35⁺ Breg differentiation in rodent malaria.

IF 4.7 2区医学 Q2 IMMUNOLOGY

International immunopharmacology Pub Date : 2025-10-30 Epub Date: 2025-08-06 DOI:10.1016/j.intimp.2025.115310

Anni Feng, Qilong Li, Ning Jiang, Kunying Lv, Yixin Yang, Tong Liu, Ziwei Su, Yiwei Zhang, Xiaoyu Sang, Ying Feng, Ran Chen, Qijun Chen

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Abstract

Augmented regulatory B cell (Breg) responses are commonly observed in malaria; however, the specific parasite components and Breg subtypes involved remain unclear. In this study, we investigated C57BL/6 mice infected with Plasmodium berghei ANKA, which induces cerebral malaria pathology, in comparison to P. yoelii YM, which does not. We found that distinct Breg types differentiated in response to these infections, driven by hemozoin-mediated Toll-like receptor 9 activation. Interleukin-35-positive (IL-35⁺) Breg expansion occurred in P. yoelii YM-infected mice but not in those infected with P. berghei ANKA. We demonstrated that stimulator of interferon genes (STING)-mediated interferon regulatory factor 3 (IRF3) phosphorylation suppressed IL-35⁺ Breg differentiation, potentially contributing to experimental cerebral malaria (ECM). In contrast, P. yoelii YM infection activated IRF3 in a STING-independent manner, promoting IL-35⁺ Breg expansion. These findings highlight IL-35⁺ Bregs as key modulators in malarial immunopathology.

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不同的STING-IRF3激活决定了IL-35+ Breg在啮齿动物疟疾中的分化。

增强的调节性B细胞（Breg）反应通常在疟疾中观察到；然而，具体的寄生虫成分和涉及的Breg亚型仍不清楚。在本研究中，我们研究了感染伯氏疟原虫ANKA的C57BL/6小鼠与未引起脑疟疾病理的P. yoelii YM的比较。我们发现在血色素蛋白介导的toll样受体9激活的驱动下，不同的Breg类型在对这些感染的反应中分化。白细胞介素-35阳性（IL-35+） Breg扩增发生在P. yoelii ym感染的小鼠中，而在P. berghei ANKA感染的小鼠中没有。我们证明干扰素基因刺激因子（STING）介导的干扰素调节因子3 （IRF3）磷酸化抑制IL-35+ Breg分化，可能有助于实验性脑性疟疾（ECM）。相比之下，P. yoelii YM感染以不依赖sting的方式激活IRF3，促进IL-35+ Breg扩增。这些发现强调了IL-35+ Bregs在疟疾免疫病理中的关键调节作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

International immunopharmacology 医学-免疫学

CiteScore

8.40

自引率

3.60%

发文量

935

审稿时长

53 days

期刊介绍： International Immunopharmacology is the primary vehicle for the publication of original research papers pertinent to the overlapping areas of immunology, pharmacology, cytokine biology, immunotherapy, immunopathology and immunotoxicology. Review articles that encompass these subjects are also welcome. The subject material appropriate for submission includes: • Clinical studies employing immunotherapy of any type including the use of: bacterial and chemical agents; thymic hormones, interferon, lymphokines, etc., in transplantation and diseases such as cancer, immunodeficiency, chronic infection and allergic, inflammatory or autoimmune disorders. • Studies on the mechanisms of action of these agents for specific parameters of immune competence as well as the overall clinical state. • Pre-clinical animal studies and in vitro studies on mechanisms of action with immunopotentiators, immunomodulators, immunoadjuvants and other pharmacological agents active on cells participating in immune or allergic responses. • Pharmacological compounds, microbial products and toxicological agents that affect the lymphoid system, and their mechanisms of action. • Agents that activate genes or modify transcription and translation within the immune response. • Substances activated, generated, or released through immunologic or related pathways that are pharmacologically active. • Production, function and regulation of cytokines and their receptors. • Classical pharmacological studies on the effects of chemokines and bioactive factors released during immunological reactions.