Peptidoglycan from the gut microbiota governs the lifespan of circulating phagocytes at homeostasis

Autor(es)

Hergott, Christopher B. ^[1] ; Roche, Aoife M. ^[1] ; Tamashiro, Edwin ^{[1, 2]} ; Clarke, Thomas B. ^[3] ; Bailey, Aubrey G. ^[1] ; Laughlin, Alice ^[1] ; Bushman, Frederic D. ^[1] ; Weiser, Jeffrey N. ^{[4, 1, 5]}

Afiliação do(s) autor(es)

^[1] Univ Penn, Dept Microbiol, Perelman Sch Med, Philadelphia, PA 19104 - USA

^[2] Univ Sao Paulo, Dept Ophthalmol Otorhinolaryngol & Head & Neck Su, Ribeirao Preto Sch Med, Sao Paulo - Brazil

^[3] Univ London Imperial Coll Sci Technol & Med, Med Res Council Ctr Mol Bacteriol & Infect, London - England

^[4] Univ Penn, Dept Pediat, Perelman Sch Med, Philadelphia, PA 19104 - USA

^[5] NYU, Sch Med, Dept Microbiol, New York, NY 10016 - USA

• Tipo de documento: Artigo Científico
• Fonte: Blood; v. 127, n. 20, p. 2460-2471, MAY 19 2016.
• Citações Web of Science: 30

Resumo

Maintenance of myeloid cell homeostasis requires continuous turnover of phagocytes from the bloodstream, yet whether environmental signals influence phagocyte longevity in the absence of inflammation remains unknown. Here, we show that the gut microbiota regulates the steady-state cellular lifespan of neutrophils and inflammatory monocytes, the 2 most abundant circulating myeloid cells and key contributors to inflammatory responses. Treatment of mice with broad-spectrum antibiotics, or with the gut-restricted aminoglycoside neomycinalone, accelerated phagocyte turnover and increased the rates of their spontaneous apoptosis. Metagenomic analyses revealed that neomycin altered the abundance of intestinal bacteria bearing gamma-D-glutamyl-meso-diaminopimelic acid, a ligand for the intracellular peptidoglycan sensor Nod1. Accordingly, signaling through Nod1 was both necessary and sufficient to mediate the stimulatory influence of the flora on myeloid cell longevity. Stimulation of Nod1 signaling increased the frequency of lymphocytes in the murine intestine producing the proinflammatory cytokine interleukin 17A (IL-17A), and liberation of IL-17A was required for transmission of Nod1-dependent signals to circulating phagocytes. Together, these results define a mechanism through which intestinal microbes govern a central component of myeloid homeostasis and suggest perturbations of commensal communities can influence steady-state regulation of cell fate. (AU)

• Processo FAPESP: 14/00027-9 - Avaliação do papel da microbiota no processo de colonização bacteriana de vias aéreas superiores
• Beneficiário: Edwin Tamashiro
• Modalidade de apoio: Bolsas no Exterior - Pesquisa