Abstract
Mycobacteria in complete Freund's adjuvant (CFA) are an essential component of immunization protocols in a number of autoimmune disease animal models including experimental autoimmune encephalomyelitis and uveoretinitis (EAE and EAU, respectively). We determined the role in EAU of two C-type lectin receptors on myeloid cells that recognize and respond to mycobacteria. Using receptor-specific antibodies and knockout mice, we demonstrated for the first time that the macrophage mannose receptor delays disease development but does not affect severity. In contrast, dectin-1 is critically involved in the development of CFA-mediated EAU. Disease severity is reduced in dectin-1 knockout mice and antibody blockade of dectin-1 during the induction, but not the effector phase, prevents EAU development. Significantly, similar blockade of dectin-1 in vivo has no effect in non-CFA-mediated, spontaneously induced or adoptive transfer models of EAU. Thus dectin-1 plays a critical role in the ability of complete Freund's adjuvant to induce EAU in mice.
| Original language | English |
|---|---|
| Pages (from-to) | 398-406 |
| Number of pages | 9 |
| Journal | Molecular Immunology |
| Volume | 67 |
| Issue number | 2 B |
| Early online date | 26 Jul 2015 |
| DOIs | |
| Publication status | Published - Oct 2015 |
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Keywords
- macrophage mannose receptor
- dectin-1
- mycobacteria
- experimental autoimmune uveitis
- pattern recognition receptor
- adjuvant
Cite this
Murine pattern recognition receptor dectin-1 is essential in the development of experimental autoimmune uveoretinitis. / Stoppelkamp, Sandra; Reid, Delyth M; Yeoh, Joyce; Taylor, Julie; McKenzie, Emma J; Brown, Gordon D; Gordon, Siamon; Forrester, John V; Wong, Simon Y C.
In: Molecular Immunology, Vol. 67, No. 2 B, 10.2015, p. 398-406.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Murine pattern recognition receptor dectin-1 is essential in the development of experimental autoimmune uveoretinitis
AU - Stoppelkamp, Sandra
AU - Reid, Delyth M
AU - Yeoh, Joyce
AU - Taylor, Julie
AU - McKenzie, Emma J
AU - Brown, Gordon D
AU - Gordon, Siamon
AU - Forrester, John V
AU - Wong, Simon Y C
N1 - Copyright © 2015. Published by Elsevier Ltd. This work was generously supported by the Wellcome Trust (GB), Cunningham Trust (JVF, DMR and SYCW), NHS Grampian Trust (SW), Tenovus Scotland (SW) and University of Aberdeen Development Trust (JVF). The funding bodies had no involvement in study design; in the collection, analysis and interpretation of data; in the writing of the report and in the decision to submit the article for publication. We also thank the technical staff at the Medical Research Facility (University of Aberdeen) for their help in maintaining the mice used in this study.
PY - 2015/10
Y1 - 2015/10
N2 - Mycobacteria in complete Freund's adjuvant (CFA) are an essential component of immunization protocols in a number of autoimmune disease animal models including experimental autoimmune encephalomyelitis and uveoretinitis (EAE and EAU, respectively). We determined the role in EAU of two C-type lectin receptors on myeloid cells that recognize and respond to mycobacteria. Using receptor-specific antibodies and knockout mice, we demonstrated for the first time that the macrophage mannose receptor delays disease development but does not affect severity. In contrast, dectin-1 is critically involved in the development of CFA-mediated EAU. Disease severity is reduced in dectin-1 knockout mice and antibody blockade of dectin-1 during the induction, but not the effector phase, prevents EAU development. Significantly, similar blockade of dectin-1 in vivo has no effect in non-CFA-mediated, spontaneously induced or adoptive transfer models of EAU. Thus dectin-1 plays a critical role in the ability of complete Freund's adjuvant to induce EAU in mice.
AB - Mycobacteria in complete Freund's adjuvant (CFA) are an essential component of immunization protocols in a number of autoimmune disease animal models including experimental autoimmune encephalomyelitis and uveoretinitis (EAE and EAU, respectively). We determined the role in EAU of two C-type lectin receptors on myeloid cells that recognize and respond to mycobacteria. Using receptor-specific antibodies and knockout mice, we demonstrated for the first time that the macrophage mannose receptor delays disease development but does not affect severity. In contrast, dectin-1 is critically involved in the development of CFA-mediated EAU. Disease severity is reduced in dectin-1 knockout mice and antibody blockade of dectin-1 during the induction, but not the effector phase, prevents EAU development. Significantly, similar blockade of dectin-1 in vivo has no effect in non-CFA-mediated, spontaneously induced or adoptive transfer models of EAU. Thus dectin-1 plays a critical role in the ability of complete Freund's adjuvant to induce EAU in mice.
KW - macrophage mannose receptor
KW - dectin-1
KW - mycobacteria
KW - experimental autoimmune uveitis
KW - pattern recognition receptor
KW - adjuvant
U2 - 10.1016/j.molimm.2015.07.002
DO - 10.1016/j.molimm.2015.07.002
M3 - Article
VL - 67
SP - 398
EP - 406
JO - Molecular Immunology
JF - Molecular Immunology
SN - 0161-5890
IS - 2 B
ER -