The C-Type Lectin Receptor CLECSF8/CLEC4D Is a Key Component of Anti-Mycobacterial Immunity

Gillian J Wilson, Mohlopheni J Marakalala, Jennifer C Hoving, Arjan van Laarhoven, Rebecca A Drummond, Bernhard Kerscher, Roanne Keeton, Esther van de Vosse, Tom H M Ottenhoff, Theo S Plantinga, Bachti Alisjahbana, Dhirendra Govender, Gurdyal S Besra, Mihai G Netea, Delyth M Reid, Janet A Willment, Muazzam Jacobs, Sho Yamasaki, Reinout van Crevel, Gordon D Brown

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Abstract

The interaction of microbes with pattern recognition receptors (PRRs) is essential for protective immunity. While many PRRs that recognize mycobacteria have been identified, none is essentially required for host defense in vivo. Here, we have identified the C-type lectin receptor CLECSF8 (CLEC4D, MCL) as a key molecule in anti-mycobacterial host defense. Clecsf8(-/-) mice exhibit higher bacterial burdens and increased mortality upon M. tuberculosis infection. Additionally, Clecsf8 deficiency is associated with exacerbated pulmonary inflammation, characterized by enhanced neutrophil recruitment. Clecsf8(-/-) mice show reduced mycobacterial uptake by pulmonary leukocytes, but infection with opsonized bacteria can restore this phagocytic defect as well as decrease bacterial burdens. Notably, a CLECSF8 polymorphism identified in humans is associated with an increased susceptibility to pulmonary tuberculosis. We conclude that CLECSF8 plays a non-redundant role in anti-mycobacterial immunity in mouse and in man.

Original languageEnglish
Pages (from-to)252-259
Number of pages8
JournalCell Host & Microbe
Volume17
Issue number2
DOIs
Publication statusPublished - 11 Feb 2015

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Wilson, G. J., Marakalala, M. J., Hoving, J. C., van Laarhoven, A., Drummond, R. A., Kerscher, B., ... Brown, G. D. (2015). The C-Type Lectin Receptor CLECSF8/CLEC4D Is a Key Component of Anti-Mycobacterial Immunity. Cell Host & Microbe, 17(2), 252-259. https://doi.org/10.1016/j.chom.2015.01.004