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Nat Nanotechnol. 2015 Apr;10(4):361-9. doi: 10.1038/nnano.2015.19. Epub 2015 Mar 9.

An endogenous nanomineral chaperones luminal antigen and peptidoglycan to intestinal immune cells.

Author information

1
Medical Research Council Human Nutrition Research, Elsie Widdowson Laboratory, Fulbourn Road, Cambridge CB1 9NL, UK.
2
Cambridge Advanced Imaging Centre, Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3DY, UK.
3
Institute for Materials Research, SPEME, University of Leeds, Leeds LS2 9JT, UK.
4
Departamento de Ciencia de los Materiales e Ingenieria Metalúrgica y Química Inorganica, Facultad de Ciencias, Universidad de Cádiz, Campus Universitario Rio San Pedro, Puerto Real (Cádiz) 11.510, Spain.
5
Department of Materials Science and Metallurgy, University of Cambridge, 27 Charles Babbage Road, Cambridge CB3 0FS, UK.
6
Technische Universitaet Dresden, Fakultaet Maschinenwesen, Institut fuer Stroemungsmechanik, Dresden 01062, Germany.
7
Ion Beam Centre, Advanced Technology Institute, Faculty of Engineering and Physical Sciences, University of Surrey, Guildford, Surrey GU2 7XH, UK.
8
1] Ion Beam Centre, Advanced Technology Institute, Faculty of Engineering and Physical Sciences, University of Surrey, Guildford, Surrey GU2 7XH, UK [2] Institute of Cancer Sciences, The University of Manchester, 27 Palatine Road, Withington, Manchester M20 3LJ, UK.
9
The Roslin Institute and Royal (Dick) School of Veterinary Sciences, University of Edinburgh, Easter Bush, Midlothian EH25 9RG, UK.
10
Department of Pathology, Emory University School of Medicine, 615 Michael Street, Atlanta, Georgia 30322, USA.
11
Department of Laboratory Medicine and Pathobiology, 1 King's College Circle, Toronto M5S 1A8, Canada.
12
1] Department of Immunology, Erasmus MC, University Medical Centre and MS Centre ErasMS, PO Box 2040, Rotterdam 3000 CA, The Netherlands [2] Department of Neuroscience, Section Medical Physiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
13
Department of Internal Medicine IV and Institute of Medical Microbiology and Hygiene, University Medical Center, Freiburg 79106, Germany.
14
Immunoregulation Laboratory, MRC Centre for Transplantation, King's College London, Guys' Hospital, London SE1 9RT, UK.
15
1] Medical Research Council Human Nutrition Research, Elsie Widdowson Laboratory, Fulbourn Road, Cambridge CB1 9NL, UK [2] Royal College of Physicians, 11 St Andrews Place, Regent's Park, London NW1 4LE, UK.

Abstract

In humans and other mammals it is known that calcium and phosphate ions are secreted from the distal small intestine into the lumen. However, why this secretion occurs is unclear. Here, we show that the process leads to the formation of amorphous magnesium-substituted calcium phosphate nanoparticles that trap soluble macromolecules, such as bacterial peptidoglycan and orally fed protein antigens, in the lumen and transport them to immune cells of the intestinal tissue. The macromolecule-containing nanoparticles utilize epithelial M cells to enter Peyer's patches, small areas of the intestine concentrated with particle-scavenging immune cells. In wild-type mice, intestinal immune cells containing these naturally formed nanoparticles expressed the immune tolerance-associated molecule 'programmed death-ligand 1', whereas in NOD1/2 double knockout mice, which cannot recognize peptidoglycan, programmed death-ligand 1 was undetected. Our results explain a role for constitutively formed calcium phosphate nanoparticles in the gut lumen and show how this helps to shape intestinal immune homeostasis.

Comment in

PMID:
25751305
PMCID:
PMC4404757
DOI:
10.1038/nnano.2015.19
[Indexed for MEDLINE]
Free PMC Article

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