Cytochalasin Z16 reshapes macrophage responses to intracellular pathogens: HSPA5-targeted immunotherapy against zoonotic and foodborne Edwardsiella tarda.
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| Natura: | Artículo científico |
| Lingua: | en |
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International immunopharmacology
2026
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| _version_ | 1868266097698930690 |
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| author | Shi, Jin-Jin Yu, Jing Wang, Ran Zhao, Hang Su, Yu-Qi Liu, Yan-Jun Chen, Ru-Yi Ding, Li-Jian Yang, Guan-Jun Chen, Jiong |
| author_facet | Shi, Jin-Jin Yu, Jing Wang, Ran Zhao, Hang Su, Yu-Qi Liu, Yan-Jun Chen, Ru-Yi Ding, Li-Jian Yang, Guan-Jun Chen, Jiong Shi, Jin-Jin Yu, Jing Wang, Ran Zhao, Hang Su, Yu-Qi Liu, Yan-Jun Chen, Ru-Yi Ding, Li-Jian Yang, Guan-Jun Chen, Jiong |
| collection | PubMed - marine biology |
| contents | Cytochalasin Z16 reshapes macrophage responses to intracellular pathogens: HSPA5-targeted immunotherapy against zoonotic and foodborne Edwardsiella tarda. Shi, Jin-Jin Yu, Jing Wang, Ran Zhao, Hang Su, Yu-Qi Liu, Yan-Jun Chen, Ru-Yi Ding, Li-Jian Yang, Guan-Jun Chen, Jiong Edwardsiella tarda Animals Humans Macrophages Endoplasmic Reticulum Chaperone BiP Cytochalasins Phagocytosis Heat-Shock Proteins Enterobacteriaceae Infections Immunotherapy Host-Directed Therapy Reactive Oxygen Species Apoptosis Foodborne Diseases Edwardsiella tarda is a zoonotic, foodborne intracellular pathogen that causes significant disease in both farmed and wild fish and can also infect humans. By surviving within macrophages, this pathogen evades immune clearance, presenting a challenge for treatment. Compound 5, a marine fungal macrocyclic lactone structurally classified among anti-inflammatory cytochalasins (formerly cytochalasin Z16) and isolated from the marine-derived fungus Aspergillus sp. NBU4698, lacks direct antibacterial activity but markedly enhances macrophage-mediated clearance of E. tarda. This compound exerts multifaceted immunomodulatory effects: it suppresses phagocytosis, pathogen-induced apoptosis, and inflammation while simultaneously promoting bacterial killing. These actions occur through dual regulation of ROS-elevating mitochondrial ROS while reducing total cellular ROS-and via modulation of the lipid droplet-antimicrobial peptide axis, which inhibits E. tarda-stimulated lipid droplet formation and CRAMP expression. Mechanistically, compound 5 targets HSPA5, a protein that appears to coordinate host defense through interactions with alpha-2-macroglobulin (A2M) and siah E3 ubiquitin protein ligase 2 (SIAH2). Our findings identify HSPA5 as a promising target for host-directed therapy and provide the first evidence for cytochalasin-based immunomodulation against intracellular bacterial pathogens. |
| format | Artículo científico |
| id | pubmed_41554224 |
| institution | PubMed |
| language | en |
| publishDate | 2026 |
| publisher | International immunopharmacology |
| record_format | pubmed |
| spellingShingle | Cytochalasin Z16 reshapes macrophage responses to intracellular pathogens: HSPA5-targeted immunotherapy against zoonotic and foodborne Edwardsiella tarda. Shi, Jin-Jin Yu, Jing Wang, Ran Zhao, Hang Su, Yu-Qi Liu, Yan-Jun Chen, Ru-Yi Ding, Li-Jian Yang, Guan-Jun Chen, Jiong Edwardsiella tarda Animals Humans Macrophages Endoplasmic Reticulum Chaperone BiP Cytochalasins Phagocytosis Heat-Shock Proteins Enterobacteriaceae Infections Immunotherapy Host-Directed Therapy Reactive Oxygen Species Apoptosis Foodborne Diseases Cytochalasin Z16 reshapes macrophage responses to intracellular pathogens: HSPA5-targeted immunotherapy against zoonotic and foodborne Edwardsiella tarda. Shi, Jin-Jin Yu, Jing Wang, Ran Zhao, Hang Su, Yu-Qi Liu, Yan-Jun Chen, Ru-Yi Ding, Li-Jian Yang, Guan-Jun Chen, Jiong Edwardsiella tarda Animals Humans Macrophages Endoplasmic Reticulum Chaperone BiP Cytochalasins Phagocytosis Heat-Shock Proteins Enterobacteriaceae Infections Immunotherapy Host-Directed Therapy Reactive Oxygen Species Apoptosis Foodborne Diseases Edwardsiella tarda is a zoonotic, foodborne intracellular pathogen that causes significant disease in both farmed and wild fish and can also infect humans. By surviving within macrophages, this pathogen evades immune clearance, presenting a challenge for treatment. Compound 5, a marine fungal macrocyclic lactone structurally classified among anti-inflammatory cytochalasins (formerly cytochalasin Z16) and isolated from the marine-derived fungus Aspergillus sp. NBU4698, lacks direct antibacterial activity but markedly enhances macrophage-mediated clearance of E. tarda. This compound exerts multifaceted immunomodulatory effects: it suppresses phagocytosis, pathogen-induced apoptosis, and inflammation while simultaneously promoting bacterial killing. These actions occur through dual regulation of ROS-elevating mitochondrial ROS while reducing total cellular ROS-and via modulation of the lipid droplet-antimicrobial peptide axis, which inhibits E. tarda-stimulated lipid droplet formation and CRAMP expression. Mechanistically, compound 5 targets HSPA5, a protein that appears to coordinate host defense through interactions with alpha-2-macroglobulin (A2M) and siah E3 ubiquitin protein ligase 2 (SIAH2). Our findings identify HSPA5 as a promising target for host-directed therapy and provide the first evidence for cytochalasin-based immunomodulation against intracellular bacterial pathogens. |
| title | Cytochalasin Z16 reshapes macrophage responses to intracellular pathogens: HSPA5-targeted immunotherapy against zoonotic and foodborne Edwardsiella tarda. |
| topic | Edwardsiella tarda Animals Humans Macrophages Endoplasmic Reticulum Chaperone BiP Cytochalasins Phagocytosis Heat-Shock Proteins Enterobacteriaceae Infections Immunotherapy Host-Directed Therapy Reactive Oxygen Species Apoptosis Foodborne Diseases |
| url | https://pubmed.ncbi.nlm.nih.gov/41554224/ |