| Autor: |
Chiaranunt, Pailin, Burrows, Kyle, Ngai, Louis, Tai, Siu Ling, Cao, Eric Y., Liang, Helen, Hamidzada, Homaira, Wong, Anthony, Gschwend, Julia, Flüchter, Pascal, Kuypers, Meggie, Despot, Tijana, Momen, Abdul, Lim, Sung Min, Mallevaey, Thierry, Schneider, Christoph, Conway, Tyrrell, Imamura, Hiromi, Epelman, Slava, Mortha, Arthur |
| Zdroj: |
Science Immunology; 2023, Vol. 8 Issue 86, p1-18, 18p |
| Abstrakt: |
Maintaining macrophage (MΦ) heterogeneity is critical to ensure intestinal tissue homeostasis and host defense. The gut microbiota and host factors are thought to synergistically guide intestinal MΦ development, although the exact nature, regulation, and location of such collaboration remain unclear. Here, we report that microbial biochemical energy metabolism promotes colony-stimulating factor 2 (CSF2) production by group 3 innate lymphoid cells (ILC3s) within solitary isolated lymphoid tissues (SILTs) in a cell-extrinsic, NLRP3/P2X7R-dependent fashion in the steady state. Tissue-infiltrating monocytes accumulating around SILTs followed a spatially constrained, distinct developmental trajectory into SILT-associated MΦs (SAMs). CSF2 regulated the mitochondrial membrane potential and reactive oxygen species production of SAMs and contributed to the antimicrobial defense against enteric bacterial infections. Collectively, these findings identify SILTs and CSF2-producing ILC3s as a microanatomic niche for intestinal MΦ development and functional programming fueled by the integration of commensal microbial energy metabolism. Editor's summary: Intestinal macrophages are a heterogenous population that contributes to gut homeostasis and host defense, but the signals regulating their development within the gut are not fully understood. Chiaranunt et al. describe a microanatomic niche in solitary isolated lymphoid tissue (SILT) that guides the differentiation of a specialized monocyte-derived macrophage population. Colonic macrophage development in SILT required CSF2-producing group 3 innate lymphoid cells and activation of P2X7R by microbiota-derived extracellular adenosine 5'-triphosphate. CSF2-dependent, SILT-associated macrophages highly expressed genes involved in energy metabolism and ROS production and were required for protection against Citrobacter rodentium infection. Together, these findings identify SILTs as a specialized niche for integrating microbial and host-derived signals to support immune defenses at the intestinal mucosa. —Claire Olingy [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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