Branched actin networks mediate macrophage-dependent host-microbiota homeostasis
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Luiz Ricardo da Costa Vasconcellos Shaina Huang Alejandro Suárez-Bonnet Simon Priestnall Probir Chakravarty Sunita Varsani-Brown Matthew L Winder Kathleen Shah Naoko Kogata Brigitta Stockinger Michael WayAbstract
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.
Journal details
Journal
Science
Volume
390
Issue number
6774
Pages
728-734
Available online
Publication date
Full text links
Publisher website (DOI)
10.1126/science.adr9571
Europe PubMed Central
41231985
Pubmed
41231985
