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Mannose receptor 1 mediates cellular uptake and endosomal delivery of CpG-motif containing oligodeoxynucleotides

Publication ,  Journal Article
Moseman, AP; Moseman, EA; Schworer, S; Smirnova, I; Volkova, T; Von Andrian, U; Poltorak, A
Published in: Journal of Immunology
December 1, 2013

Recognition of microbial components is critical for activation of TLRs, subsequent innate immune signaling, and directing adaptive immune responses. The DNA sensor TLR9 traffics from the endoplasmic reticulum to endolysosomal compartments where it is cleaved by resident proteases to generate a competent receptor. Activation of TLR9 by CpG-motif containing oligodeoxynucleotides (CpG ODNs) is preceded by agonist endocytosis and delivery into the endolysosomes. The events that dictate this process remain largely unknown; furthermore, it is unclear whether the receptors involved in mediating uptake of exogenous DNA are conserved for both naturally derived pathogenic DNA and synthetic ODNs. In this study, we report that peritoneal macrophages from a wild-derived inbred mouse strain, MOLF/Ei, are hyporesponsive to CpG ODN but are fully responsive to bacterial DNA, thus implying that microbial recognition is not fully recapitulated by a synthetic analog. To identify the gene responsible for the CpG ODN defect, we have performed genome-wide linkage analysis. Using N2 backcross mice, we mapped the trait with high resolution to a single locus containing Mrc1 as the gene conferring the trait. We show that mannose receptor 1 (MRC1; CD206) is involved in CpG ODN uptake and trafficking in wild-derived MOLF/Ei peritoneal macrophages. Furthermore, we show that other strains of wild-derived mice also require MRC1 for CpG-induced cytokine responses. These findings reveal novel functions for MRC1 and demonstrate that wild-derived mice are important and indispensable model for understanding naturally occurring regulators of inflammatory responses in innate immune pathways. Copyright © 2013 by The American Association of Immunologists, Inc.

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Published In

Journal of Immunology

DOI

EISSN

1550-6606

ISSN

0022-1767

Publication Date

December 1, 2013

Volume

191

Issue

11

Start / End Page

5615 / 5624

Related Subject Headings

  • Immunology
  • 3204 Immunology
  • 3101 Biochemistry and cell biology
  • 1107 Immunology
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Moseman, A. P., Moseman, E. A., Schworer, S., Smirnova, I., Volkova, T., Von Andrian, U., & Poltorak, A. (2013). Mannose receptor 1 mediates cellular uptake and endosomal delivery of CpG-motif containing oligodeoxynucleotides. Journal of Immunology, 191(11), 5615–5624. https://doi.org/10.4049/jimmunol.1301438
Moseman, A. P., E. A. Moseman, S. Schworer, I. Smirnova, T. Volkova, U. Von Andrian, and A. Poltorak. “Mannose receptor 1 mediates cellular uptake and endosomal delivery of CpG-motif containing oligodeoxynucleotides.” Journal of Immunology 191, no. 11 (December 1, 2013): 5615–24. https://doi.org/10.4049/jimmunol.1301438.
Moseman AP, Moseman EA, Schworer S, Smirnova I, Volkova T, Von Andrian U, et al. Mannose receptor 1 mediates cellular uptake and endosomal delivery of CpG-motif containing oligodeoxynucleotides. Journal of Immunology. 2013 Dec 1;191(11):5615–24.
Moseman, A. P., et al. “Mannose receptor 1 mediates cellular uptake and endosomal delivery of CpG-motif containing oligodeoxynucleotides.” Journal of Immunology, vol. 191, no. 11, Dec. 2013, pp. 5615–24. Scopus, doi:10.4049/jimmunol.1301438.
Moseman AP, Moseman EA, Schworer S, Smirnova I, Volkova T, Von Andrian U, Poltorak A. Mannose receptor 1 mediates cellular uptake and endosomal delivery of CpG-motif containing oligodeoxynucleotides. Journal of Immunology. 2013 Dec 1;191(11):5615–5624.

Published In

Journal of Immunology

DOI

EISSN

1550-6606

ISSN

0022-1767

Publication Date

December 1, 2013

Volume

191

Issue

11

Start / End Page

5615 / 5624

Related Subject Headings

  • Immunology
  • 3204 Immunology
  • 3101 Biochemistry and cell biology
  • 1107 Immunology