title: The C-type lectin receptor CLECSF8/CLEC4D is a key component of anti-mycobacterial immunity.
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.
authors: Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK.
authors: Gillian J
authors: GJ
authors: Wilson
authors: Division of Immunology, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, 792 Cape Town, South Africa.
authors: Mohlopheni J
authors: MJ
authors: Marakalala
authors: Division of Immunology, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, 792 Cape Town, South Africa.
authors: Jennifer C
authors: JC
authors: Hoving
authors: Department of Internal Medicine, Radboud University Medical Center, Nijmegen 6525 GA, the Netherlands.
authors: Arjan
authors: A
authors: van Laarhoven
authors: Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK.
authors: Rebecca A
authors: RA
authors: Drummond
authors: Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK.
authors: Bernhard
authors: B
authors: Kerscher
authors: Division of Immunology, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, 792 Cape Town, South Africa.
authors: Roanne
authors: R
authors: Keeton
authors: Department of Infectious Diseases, Leiden University Medical Center, Leiden 2333 ZA, the Netherlands.
authors: Esther
authors: E
authors: van de Vosse
authors: Department of Infectious Diseases, Leiden University Medical Center, Leiden 2333 ZA, the Netherlands.
authors: Tom H M
authors: TH
authors: Ottenhoff
authors: Department of Internal Medicine, Radboud University Medical Center, Nijmegen 6525 GA, the Netherlands.
authors: Theo S
authors: TS
authors: Plantinga
authors: Health Research Unit, Universitas Padjadjaran, Bandung 40161, Indonesia.
authors: Bachti
authors: B
authors: Alisjahbana
authors: Division of Anatomical Pathology, University of Cape Town, 7925 Cape Town, South Africa.
authors: Dhirendra
authors: D
authors: Govender
authors: School of Biosciences, University of Birmingham, Birmingham B15 2TT, UK.
authors: Gurdyal S
authors: GS
authors: Besra
authors: Department of Internal Medicine, Radboud University Medical Center, Nijmegen 6525 GA, the Netherlands.
authors: Mihai G
authors: MG
authors: Netea
authors: Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK.
authors: Delyth M
authors: DM
authors: Reid
authors: Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK.
authors: Janet A
authors: JA
authors: Willment
authors: Division of Immunology, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, 792 Cape Town, South Africa.
authors: Muazzam
authors: M
authors: Jacobs
authors: Division of Molecular Immunology, Medical Institute of Bioregulation, Kyushu University, Fukuoka 108-8639, Japan.
authors: Sho
authors: S
authors: Yamasaki
authors: Department of Internal Medicine, Radboud University Medical Center, Nijmegen 6525 GA, the Netherlands.
authors: Reinout
authors: R
authors: van Crevel
authors: Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK; Division of Immunology, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, 792 Cape Town, South Africa. Electronic address: gordon.brown@abdn.ac.uk.
authors: Gordon D
authors: GD
authors: Brown
mesh_terms: D000818:Animals; D058491:Bacterial Load; D004195:Disease Models, Animal; D020022:Genetic Predisposition to Disease; D006801:Humans; D037181:Lectins, C-Type / Q000378:metabolism*; D008168:Lung / Q000473:pathology; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology; D010587:Phagocytosis; D011110:Polymorphism, Genetic; D011971:Receptors, Immunologic / Q000378:metabolism; D016019:Survival Analysis; D014397:Tuberculosis, Pulmonary / Q000276:immunology / Q000382:microbiology / Q000473:pathology
chemical_list: C482593:CLEC4D protein, human; C113583:Clecsf8 protein, mouse; D037181:Lectins, C-Type; D008565:Membrane Proteins; D011971:Receptors, Immunologic