Constant Replenishment from Circulating Monocytes Maintains the Macrophage Pool in the Intestine of Adult Mice

Overview

Journal Nat Immunol

Date 2014 Aug 25

PMID 25151491

Citations 572

Authors

Calum C Bain

Alberto Bravo-Blas

Charlotte L Scott

Elisa Gomez Perdiguero

Frederic Geissmann

Sandrine Henri

Bernard Malissen

Lisa C Osborne

David Artis

Allan McI Mowat

Affiliations

Soon will be listed here.

Abstract

The paradigm that macrophages that reside in steady-state tissues are derived from embryonic precursors has never been investigated in the intestine, which contains the largest pool of macrophages. Using fate-mapping models and monocytopenic mice, together with bone marrow chimera and parabiotic models, we found that embryonic precursor cells seeded the intestinal mucosa and demonstrated extensive in situ proliferation during the neonatal period. However, these cells did not persist in the intestine of adult mice. Instead, they were replaced around the time of weaning by the chemokine receptor CCR2-dependent influx of Ly6C(hi) monocytes that differentiated locally into mature, anti-inflammatory macrophages. This process was driven largely by the microbiota and had to be continued throughout adult life to maintain a normal intestinal macrophage pool.

Citing Articles

Immune Alterations and Viral Reservoir Atlas in SIV-Infected Chinese Rhesus Macaques.

Clain J, Picard M, Rabezanahary H, Andre S, Boutrais S, Goma Matsetse E Infect Dis Rep. 2025; 17(1).

PMID: 39997464 PMC: 11855486. DOI: 10.3390/idr17010012.

Gut-derived macrophages link intestinal damage to brain injury after cardiac arrest through TREM1 signaling.

Chang Y, Chen J, Peng Y, Zhang K, Zhang Y, Zhao X Cell Mol Immunol. 2025; .

PMID: 39984674 DOI: 10.1038/s41423-025-01263-0.

Origin, Function, and Implications of Intestinal and Hepatic Macrophages in the Pathogenesis of Alcohol-Associated Liver Disease.

Hu Y, Schnabl B, Starkel P Cells. 2025; 14(3).

PMID: 39936998 PMC: 11816606. DOI: 10.3390/cells14030207.

IL-1β enhances susceptibility to atrial fibrillation in mice by acting through resident macrophages and promoting caspase-1 expression.

Moreno-Loaiza O, Soares V, de Assumpcao Souza M, Vera-Nunez N, Rodriguez de Yurre Guirao A, da Silva T Nat Cardiovasc Res. 2025; .

PMID: 39915330 DOI: 10.1038/s44161-025-00610-8.

The Yin-Yang functions of macrophages in metabolic disorders.

Bai J, Liu F Life Med. 2025; 1(3):319-332.

PMID: 39872753 PMC: 11749365. DOI: 10.1093/lifemedi/lnac035.

References

Nagashima R, Maeda K, Imai Y, Takahashi T . Lamina propria macrophages in the human gastrointestinal mucosa: their distribution, immunohistological phenotype, and function. J Histochem Cytochem. 1996; 44(7):721-31. DOI: 10.1177/44.7.8675993. View

Davies L, Jenkins S, Allen J, Taylor P . Tissue-resident macrophages. Nat Immunol. 2013; 14(10):986-95. PMC: 4045180. DOI: 10.1038/ni.2705. View

Bertrand J, Chi N, Santoso B, Teng S, Stainier D, Traver D . Haematopoietic stem cells derive directly from aortic endothelium during development. Nature. 2010; 464(7285):108-11. PMC: 2858358. DOI: 10.1038/nature08738. View

Bogunovic M, Ginhoux F, Helft J, Shang L, Hashimoto D, Greter M . Origin of the lamina propria dendritic cell network. Immunity. 2009; 31(3):513-25. PMC: 2778256. DOI: 10.1016/j.immuni.2009.08.010. View

Ginhoux F, Liu K, Helft J, Bogunovic M, Greter M, Hashimoto D . The origin and development of nonlymphoid tissue CD103+ DCs. J Exp Med. 2009; 206(13):3115-30. PMC: 2806447. DOI: 10.1084/jem.20091756. View

Jakubzick C, Gautier E, Gibbings S, Sojka D, Schlitzer A, Johnson T . Minimal differentiation of classical monocytes as they survey steady-state tissues and transport antigen to lymph nodes. Immunity. 2013; 39(3):599-610. PMC: 3820017. DOI: 10.1016/j.immuni.2013.08.007. View

Saederup N, Cardona A, Croft K, Mizutani M, Cotleur A, Tsou C . Selective chemokine receptor usage by central nervous system myeloid cells in CCR2-red fluorescent protein knock-in mice. PLoS One. 2010; 5(10):e13693. PMC: 2965160. DOI: 10.1371/journal.pone.0013693. View

Ueda Y, Kayama H, Jeon S, Kusu T, Isaka Y, Rakugi H . Commensal microbiota induce LPS hyporesponsiveness in colonic macrophages via the production of IL-10. Int Immunol. 2010; 22(12):953-62. DOI: 10.1093/intimm/dxq449. View

Liu K, Waskow C, Liu X, Yao K, Hoh J, Nussenzweig M . Origin of dendritic cells in peripheral lymphoid organs of mice. Nat Immunol. 2007; 8(6):578-83. DOI: 10.1038/ni1462. View

10.

Davies L, Rosas M, Smith P, Fraser D, Jones S, Taylor P . A quantifiable proliferative burst of tissue macrophages restores homeostatic macrophage populations after acute inflammation. Eur J Immunol. 2011; 41(8):2155-64. DOI: 10.1002/eji.201141817. View

11.

Grimm M, Pullman W, Bennett G, Sullivan P, Pavli P, Doe W . Direct evidence of monocyte recruitment to inflammatory bowel disease mucosa. J Gastroenterol Hepatol. 1995; 10(4):387-95. DOI: 10.1111/j.1440-1746.1995.tb01589.x. View

12.

Serbina N, Pamer E . Monocyte emigration from bone marrow during bacterial infection requires signals mediated by chemokine receptor CCR2. Nat Immunol. 2006; 7(3):311-7. DOI: 10.1038/ni1309. View

13.

Hashimoto D, Chow A, Noizat C, Teo P, Beasley M, Leboeuf M . Tissue-resident macrophages self-maintain locally throughout adult life with minimal contribution from circulating monocytes. Immunity. 2013; 38(4):792-804. PMC: 3853406. DOI: 10.1016/j.immuni.2013.04.004. View

14.

Muller A, Kaiser P, Dittmar K, Weber T, Haueter S, Endt K . Salmonella gut invasion involves TTSS-2-dependent epithelial traversal, basolateral exit, and uptake by epithelium-sampling lamina propria phagocytes. Cell Host Microbe. 2012; 11(1):19-32. DOI: 10.1016/j.chom.2011.11.013. View

15.

Hill D, Hoffmann C, Abt M, Du Y, Kobuley D, Kirn T . Metagenomic analyses reveal antibiotic-induced temporal and spatial changes in intestinal microbiota with associated alterations in immune cell homeostasis. Mucosal Immunol. 2009; 3(2):148-58. PMC: 2824244. DOI: 10.1038/mi.2009.132. View

16.

Mildner A, Schmidt H, Nitsche M, Merkler D, Hanisch U, Mack M . Microglia in the adult brain arise from Ly-6ChiCCR2+ monocytes only under defined host conditions. Nat Neurosci. 2007; 10(12):1544-53. DOI: 10.1038/nn2015. View

17.

Bain C, Mowat A . CD200 receptor and macrophage function in the intestine. Immunobiology. 2011; 217(6):643-51. DOI: 10.1016/j.imbio.2011.11.004. View

18.

Yona S, Kim K, Wolf Y, Mildner A, Varol D, Breker M . Fate mapping reveals origins and dynamics of monocytes and tissue macrophages under homeostasis. Immunity. 2013; 38(1):79-91. PMC: 3908543. DOI: 10.1016/j.immuni.2012.12.001. View

19.

Epelman S, Lavine K, Randolph G . Origin and functions of tissue macrophages. Immunity. 2014; 41(1):21-35. PMC: 4470379. DOI: 10.1016/j.immuni.2014.06.013. View

20.

Chorro L, Sarde A, Li M, Woollard K, Chambon P, Malissen B . Langerhans cell (LC) proliferation mediates neonatal development, homeostasis, and inflammation-associated expansion of the epidermal LC network. J Exp Med. 2009; 206(13):3089-100. PMC: 2806478. DOI: 10.1084/jem.20091586. View