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Norway

PMID:25751305  

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

Jonathan J Powell | Emma Thomas-McKay | Vinay Thoree | Jack Robertson | Rachel E Hewitt | Jeremy N Skepper | Andy Brown | Juan Carlos Hernandez-Garrido | Paul A Midgley | Inmaculada Gomez-Morilla | Geoffrey W Grime | Karen J Kirkby | Neil A Mabbott | David S Donaldson | Ifor R Williams | Daniel Rios | Stephen E Girardin | Carolin T Haas | Sylvaine F A Bruggraber | Jon D Laman | Yakup Tanriver | Giovanna Lombardi | Robert Lechler | Richard P H Thompson | Laetitia C Pele
Nature nanotechnology | 2015

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.

Pubmed ID: 25751305

Research resources used in this publication

None found

Antibodies used in this publication

None found

Associated grants

  • Agency: Biotechnology and Biological Sciences Research Council, United Kingdom
    Id: BB/J014672/1
  • Agency: NIAID NIH HHS, United States
    Id: R21 AI111388
  • Agency: NIAID NIH HHS, United States
    Id: AI111388
  • Agency: Medical Research Council, United Kingdom
    Id: MR/J006742/1
  • Agency: NIDDK NIH HHS, United States
    Id: R01 DK064730
  • Agency: NIDDK NIH HHS, United States
    Id: DK064730
  • Agency: Medical Research Council, United Kingdom
    Id: MC_U105960399

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C57BL/6J (tool)

RRID:IMSR_JAX:000664

Mus musculus with name C57BL/6J from IMSR.

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B6.129P2-Nod1tm1Inoh/MakJ (tool)

RRID:IMSR_JAX:031732

Mus musculus with name B6.129P2-Nod1tm1Inoh/MakJ from IMSR.

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BALB/cAnNCrl (tool)

RRID:MGI:2683685

laboratory mouse with name BALB/cAnNCrl from MGI.

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