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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C-Type Lectins
Pattern Recognition Receptors
Immunity
Neutrophil Infiltration
Mycobacterium
Infection
Pulmonary Tuberculosis
Pneumonia
Tuberculosis
Leukocytes
Bacteria
Lung
Mortality

Cite this

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

The C-Type Lectin Receptor CLECSF8/CLEC4D Is a Key Component of Anti-Mycobacterial Immunity. / Wilson, Gillian J; Marakalala, Mohlopheni J; Hoving, Jennifer C; van Laarhoven, Arjan; Drummond, Rebecca A; Kerscher, Bernhard; Keeton, Roanne; van de Vosse, Esther; Ottenhoff, Tom H M; Plantinga, Theo S; Alisjahbana, Bachti; Govender, Dhirendra; Besra, Gurdyal S; Netea, Mihai G; Reid, Delyth M; Willment, Janet A; Jacobs, Muazzam; Yamasaki, Sho; van Crevel, Reinout; Brown, Gordon D.

In: Cell Host & Microbe, Vol. 17, No. 2, 11.02.2015, p. 252-259.

Research output: Contribution to journalArticle

Wilson, GJ, Marakalala, MJ, Hoving, JC, van Laarhoven, A, Drummond, RA, Kerscher, B, Keeton, R, van de Vosse, E, Ottenhoff, THM, Plantinga, TS, Alisjahbana, B, Govender, D, Besra, GS, Netea, MG, Reid, DM, Willment, JA, Jacobs, M, Yamasaki, S, van Crevel, R & Brown, GD 2015, 'The C-Type Lectin Receptor CLECSF8/CLEC4D Is a Key Component of Anti-Mycobacterial Immunity', Cell Host & Microbe, vol. 17, no. 2, pp. 252-259. https://doi.org/10.1016/j.chom.2015.01.004
Wilson GJ, Marakalala MJ, Hoving JC, van Laarhoven A, Drummond RA, Kerscher B et al. The C-Type Lectin Receptor CLECSF8/CLEC4D Is a Key Component of Anti-Mycobacterial Immunity. Cell Host & Microbe. 2015 Feb 11;17(2):252-259. https://doi.org/10.1016/j.chom.2015.01.004
Wilson, Gillian J ; Marakalala, Mohlopheni J ; Hoving, Jennifer C ; van Laarhoven, Arjan ; Drummond, Rebecca A ; Kerscher, Bernhard ; Keeton, Roanne ; van de Vosse, Esther ; Ottenhoff, Tom H M ; Plantinga, Theo S ; Alisjahbana, Bachti ; Govender, Dhirendra ; Besra, Gurdyal S ; Netea, Mihai G ; Reid, Delyth M ; Willment, Janet A ; Jacobs, Muazzam ; Yamasaki, Sho ; van Crevel, Reinout ; Brown, Gordon D. / The C-Type Lectin Receptor CLECSF8/CLEC4D Is a Key Component of Anti-Mycobacterial Immunity. In: Cell Host & Microbe. 2015 ; Vol. 17, No. 2. pp. 252-259.
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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.",
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AU - van Crevel, Reinout

AU - Brown, Gordon D

N1 - Open Access funded by Wellcome Trust: Under a Creative Commons license Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved. Acknowledgments We would like to thank S. Hardison, P. Redelinghuys, J. Taylor, C. Wallace, A. Richmond, S. Hadebe, A. Plato, F. Abbass, L. Fick, N. Allie, R. Wilkinson, K. Wilkinson, S. Cooper, D. Lang, and V. Kumar for reagents and assistance, and the animal facility staff for the care of our animals. This work was supported by the MRC (UK) and Wellcome Trust (G.D.B.); MRC (South Africa) and Sydney Brenner Fellowship (M.J.M.); Vici (M.G.N.), Vidi (R.v.C.), and Veni grants (T.S.P.) from the Netherlands Organization for Scientific Research; the Royal Netherlands Academy of Arts and Sciences (T.H.M.O.); EC FP7 projects (NEWTBVAC, ADITEC; T.H.M.O.); Carnegie Corporation and CIDRI (J.C.H.); and the University of Aberdeen (B.K.).

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