Characterization of the receptors for mycobacterial cord factor in Guinea pig

PLoS One. 2014 Feb 12;9(2):e88747. doi: 10.1371/journal.pone.0088747. eCollection 2014.

Abstract

Guinea pig is a widely used animal for research and development of tuberculosis vaccines, since its pathological disease process is similar to that present in humans. We have previously reported that two C-type lectin receptors, Mincle (macrophage inducible C-type lectin, also called Clec4e) and MCL (macrophage C-type lectin, also called Clec4d), recognize the mycobacterial cord factor, trehalose-6,6'-dimycolate (TDM). Here, we characterized the function of the guinea pig homologue of Mincle (gpMincle) and MCL (gpMCL). gpMincle directly bound to TDM and transduced an activating signal through ITAM-bearing adaptor molecule, FcRγ. Whereas, gpMCL lacked C-terminus and failed to bind to TDM. mRNA expression of gpMincle was detected in the spleen, lymph nodes and peritoneal macrophages and it was strongly up-regulated upon stimulation of zymosan and TDM. The surface expression of gpMincle was detected on activated macrophages by a newly established monoclonal antibody that also possesses a blocking activity. This antibody potently suppressed TNF production in BCG-infected macrophages. Collectively, gpMincle is the TDM receptor in the guinea pig and TDM-Mincle axis is involved in host immune responses against mycobacteria.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology
  • Cord Factors / metabolism*
  • Female
  • Gene Expression Regulation
  • Guinea Pigs
  • Lectins, C-Type / genetics
  • Lectins, C-Type / immunology
  • Lectins, C-Type / metabolism*
  • Macrophage Activation
  • Macrophages / immunology
  • Macrophages / metabolism
  • Mycobacterium bovis / metabolism*
  • Mycobacterium tuberculosis / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, Fc / metabolism

Substances

  • Antibodies, Monoclonal
  • Cord Factors
  • Lectins, C-Type
  • RNA, Messenger
  • Receptors, Fc

Grants and funding

This work was supported by Funding Program for Next Generation World-Leading Researchers (NEXT Program), Takeda Science Foundation, the Uehara Memorial foundation, Grant-in-Aid for Young Scientists (B) and the Uehara Memorial foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.