Branched actin networks mediate macrophage-dependent host-microbiota homeostasis.
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| Title: | Branched actin networks mediate macrophage-dependent host-microbiota homeostasis. |
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| Authors: | Vasconcellos, Luiz Ricardo C. (AUTHOR), Huang, Shaina Chor Mei (AUTHOR), Suarez-Bonnet, Alejandro (AUTHOR), Priestnall, Simon (AUTHOR), Chakravarty, Probir (AUTHOR), Varsani-Brown, Sunita (AUTHOR), Winder, Matthew L. (AUTHOR), Shah, Kathleen (AUTHOR), Kogata, Naoko (AUTHOR), Stockinger, Brigitta (AUTHOR), Way, Michael (AUTHOR) |
| Source: | Science. 11/13/2025, Vol. 390 Issue 6774, p728-734. 7p. |
| Subjects: | Macrophages, Immune system, Cytoskeleton, Actin, Phagocytosis, Inflammatory bowel diseases, Microfilament proteins, Microbial communities |
| Abstract: | Branched actin networks formed by the Arp2/3 complex are essential for immune system function. Patients with loss-of-function mutations in the ARPC5 subunit of the Arp2/3 complex develop inflammation and immunodeficiency after birth, leading to early mortality. The basis for these phenotypes remains obscure. We found that loss of ARPC5, but not the ARPC5L isoform, in the mouse hematopoietic system caused early-onset intestinal inflammation after weaning. This condition was initiated by microbiota breaching the ileal mucosa and led to systemic inflammation. ARPC5-deficient macrophages and neutrophils infiltrated the ileum but failed to restrict microbial invasion. Specifically, macrophages that lack ARPC5 struggled to phagocytose and kill intracellular bacteria. Our results highlight the indispensable role of ARPC5-containing, but not ARPC5L-containing, Arp2/3 complexes in mononuclear phagocyte function and host-microbiota homeostasis. Editor's summary: Reorganization of actin filaments is vital for cells to modify their shape and to migrate. Vasconcellos et al. examined the role of ARPC5, a protein subunit of the Arp2/3 complex that regulates branching of the actin cytoskeleton. Like humans with mutations in ARPC5, mice that lacked ARPC5 in hematopoietic cells were predisposed to inflammation in early life, exhibiting indicators of systemic inflammation and localized inflammation in the small intestine. This was associated with changes to the intestinal microbiota after weaning and impaired function of macrophages. Loss of ARPC5 did not compromise the ability of macrophages to migrate but did reduce their ability to phagocytose and kill bacteria. Deletion of ARPC5L, an isoform of ARPC5, in hematopoietic cells did not result in inflammation, highlighting that Arp2/3 complexes with different compositions have distinctive functions. —Sarah H. Ross [ABSTRACT FROM AUTHOR] |
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| Database: | Psychology and Behavioral Sciences Collection |
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| Abstract: | Branched actin networks formed by the Arp2/3 complex are essential for immune system function. Patients with loss-of-function mutations in the ARPC5 subunit of the Arp2/3 complex develop inflammation and immunodeficiency after birth, leading to early mortality. The basis for these phenotypes remains obscure. We found that loss of ARPC5, but not the ARPC5L isoform, in the mouse hematopoietic system caused early-onset intestinal inflammation after weaning. This condition was initiated by microbiota breaching the ileal mucosa and led to systemic inflammation. ARPC5-deficient macrophages and neutrophils infiltrated the ileum but failed to restrict microbial invasion. Specifically, macrophages that lack ARPC5 struggled to phagocytose and kill intracellular bacteria. Our results highlight the indispensable role of ARPC5-containing, but not ARPC5L-containing, Arp2/3 complexes in mononuclear phagocyte function and host-microbiota homeostasis. Editor's summary: Reorganization of actin filaments is vital for cells to modify their shape and to migrate. Vasconcellos et al. examined the role of ARPC5, a protein subunit of the Arp2/3 complex that regulates branching of the actin cytoskeleton. Like humans with mutations in ARPC5, mice that lacked ARPC5 in hematopoietic cells were predisposed to inflammation in early life, exhibiting indicators of systemic inflammation and localized inflammation in the small intestine. This was associated with changes to the intestinal microbiota after weaning and impaired function of macrophages. Loss of ARPC5 did not compromise the ability of macrophages to migrate but did reduce their ability to phagocytose and kill bacteria. Deletion of ARPC5L, an isoform of ARPC5, in hematopoietic cells did not result in inflammation, highlighting that Arp2/3 complexes with different compositions have distinctive functions. —Sarah H. Ross [ABSTRACT FROM AUTHOR] |
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| ISSN: | 00368075 |
| DOI: | 10.1126/science.adr9571 |
