Evolutionarily conserved recognition and innate immunity to fungal pathogens by the scavenger receptors SCARF1 and CD36.
Receptors involved in innate immunity to fungal pathogens have not been fully elucidated. We show that the Caenorhabditis elegans receptors CED-1 and C03F11.3, and their mammalian orthologues, the scavenger receptors SCARF1 and CD36, mediate host defense against two prototypic fungal pathogens, Cryptococcus neoformans and Candida albicans. CED-1 and C03F11.1 mediated antimicrobial peptide production and were necessary for nematode survival after C. neoformans infection. SCARF1 and CD36 mediated cytokine production and were required for macrophage binding to C. neoformans, and control of the infection in mice. Binding of these pathogens to SCARF1 and CD36 was beta-glucan dependent. Thus, CED-1/SCARF1 and C03F11.3/CD36 are beta-glucan binding receptors and define an evolutionarily conserved pathway for the innate sensing of fungal pathogens.
Means
Terry K
TK
Center for Immunology and Inflammatory Diseases and Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA. tmeans@partners.org
Mylonakis
Eleftherios
E
Tampakakis
Emmanouil
E
Colvin
Richard A
RA
Seung
Edward
E
Puckett
Lindsay
L
Tai
Melissa F
MF
Stewart
Cameron R
CR
Pukkila-Worley
Read
R
Hickman
Suzanne E
SE
Moore
Kathryn J
KJ
Calderwood
Stephen B
SB
Hacohen
Nir
N
Luster
Andrew D
AD
El Khoury
Joseph
J
D000818:Animals; D018955:CD36 Antigens / Q000172:deficiency / Q000276:immunology; D017173:Caenorhabditis elegans / Q000276:immunology / Q000382:microbiology*; D029742:Caenorhabditis elegans Proteins / Q000276:immunology; D002176:Candida albicans / Q000166:cytology / Q000276:immunology*; D002177:Candidiasis / Q000276:immunology / Q000382:microbiology; D002448:Cell Adhesion; D017124:Conserved Sequence; D003453:Cryptococcosis / Q000276:immunology / Q000382:microbiology; D003455:Cryptococcus neoformans / Q000166:cytology / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D019143:Evolution, Molecular; D007113:Immunity, Innate; D008262:Macrophage Activation; D008264:Macrophages / Q000166:cytology / Q000276:immunology / Q000382:microbiology; D008565:Membrane Proteins / Q000276:immunology; D051379:Mice; D034741:RNA, Small Interfering / Q000378:metabolism; D051116:Receptors, Scavenger / Q000276:immunology*; D016019:Survival Analysis; D051195:Toll-Like Receptor 2 / Q000378:metabolism
D018955:CD36 Antigens; D029742:Caenorhabditis elegans Proteins; D016207:Cytokines; D008565:Membrane Proteins; D034741:RNA, Small Interfering; D051116:Receptors, Scavenger; D051195:Toll-Like Receptor 2; C422043:ced-1 protein, C elegans