SCIENCE
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2025
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IF 45.8
Zhifeng Zeng,Zeyu Hu,Ruiliang Zhao,Jikai Rao,Mario Rodríguez Mestre,Yanqiu Liu,Shunhang Liu,Hao Feng,Yu Chen,Huan He,Nuo Chen,Jinshui Zheng,Donghai Peng,Min Luo,Qunxin She,Rafael Pinilla-Redondo,Wenyuan Han
Signaling from pathogen sensing to effector activation is a fundamental principle of cellular immunity. While cyclic (oligo)nucleotides have emerged as key signaling molecules, the existence of other messengers remains largely unexplored. Here, we reveal a bacterial anti-phage system that mediates immune signaling through nucleobase modification. Immunity is triggered by phage nucleotide kinases, which, combined with the system-encoded adenosine deaminase, produce deoxyinosine 5′-triphosphate (dITP) as immune messengers. The dITP signal activates downstream effector to mediate cellular NAD+ depletion, resulting in population-level defense through the death of infected cells. To counteract immune signaling, phages deploy specialized enzymes that deplete cellular dAMP, the precursor of dITP messengers. Our findings uncover a nucleobase modification-based anti-phage signaling pathway, establishing noncanonical nucleotides as a new type of immune messengers in bacteria.
研究领域:
微生物学
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免疫学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Food Frontiers
·
2024
·
IF 7.4
Ying Yang,Mengfan Luo,Wanyi Zhou,Wenyang Tao,Jingrui Li,Jianrong Xing,Quanqin Tan,Yuxing Guo
In recent years, the development of immunosuppression has become common, and probiotics are a vital immunomodulatory strategy. This study evaluated the alleviating effect of Lactiplantibacillus plantarum ( L. plantarum ) YY-112 on cyclophosphamide-induced immune imbalance and resolved the possible mechanism of action. L. plantarum YY-112 at 10 9 CFU/mL lowered loss of body weight and alleviated splenic injury, intestinal injury, and inflammation, according to the hematoxylin and eosin staining. Biochemical results showed that 10 9 CFU/mL L. plantarum YY-112 increased interleukin-10 and immunoglobulin M levels and decreased interferon-γ levels. Additionally, the immunoregulatory effect at the molecular levels of L. plantarum YY-112 was analyzed by transcriptome sequencing. L. plantarum YY-112 significantly upregulated Cr2 and downregulated C5aR1 to regulate the complement system; downregulated S100a8 , S100a9 , and Mmp9 to inhibit neutrophil aggregation; upregulated Cd19 , Cd72 , Cd3e , Cd28 , Cd80 , Cd8a , and histocompatibility-2-related genes to regulate B- and T-cell activation; and upregulated Xiap , Malt1 , Ikbkb , Mapk11 , Mef2c , Mapk12 , Ras , and Myc to activate immune signaling pathways. Furthermore, L. plantarum YY-112 improved intestinal microbial structure and reduced enrichment of Lachnospiraceae_NK4A136_group , norank_f_Lachnospiraceae , Desulfovibrio , Colidextribacter , and Helicobacter . In conclusion, these findings offer valuable insights into the potential mechanisms through which L. plantarum YY-112 regulates immune imbalance.
研究领域:
免疫学
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微生物学
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分子生物学
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药理学
✓ 已验证
产品关联
DOI
高影响因子
NEURON
·
2024
·
IF 14.7
Bin Wu,Ling Meng,Yan Zhao,Junjie Li,Qiuyun Tian,Yayan Pang,Chunguang Ren,Zhifang Dong
Social creatures must attend to threat signals from conspecifics and respond appropriately, both behaviorally and physiologically. In this work, we show in mice a threat-sensitive immune mechanism that orchestrates psychological processes and is amenable to social modulation. Repeated encounters with socially cued threats triggered meningeal neutrophil (MN) priming preferentially in males. MN activity was correlated with attenuated defensive responses to cues. Canonical neutrophil-specific activation marker CD177 was upregulated after social threat cueing, and its genetic ablation abrogated male behavioral phenotypes. CD177 signals favored meningeal T helper (Th)1-like immune bias, which blunted neural response to threatening stimuli by enhancing intrinsic GABAergic inhibition within the prelimbic cortex via interferon-gamma (IFN-γ). MN signaling was sensitized by negative emotional states and governed by socially dependent androgen release. This male-biased hormone/neutrophil regulatory axis is seemingly conserved in humans. Our findings provide insights into how immune responses influence behavioral threat responses, suggesting a possible neuroimmune basis of emotional regulation.
研究领域:
神经科学
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免疫学
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行为科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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