Dectin-1 is required for human dendritic cells to initiate immune response to Candida albicans through Syk activation.
Dectin-1 is a pattern recognition receptor found on monocytes and dendritic cells (DC) able to recognize beta-1,3 and beta-1,6 glucans. It is thought to act via the spleen tyrosine kinase (Syk) to initiate immune response against infectious agents such as Candida albicans, one of the leading causes of invasive fungal disease in immunocompromised individuals. This study addresses the importance of this receptor in the context of human DC response to C. albicans. Upon blockage of Dectin-1, immature DC are less able than untreated cells to bind, phagocytose, and kill C. albicans via oxidative burst. In fact, a consistent decrease in superoxide anion, but not nitric oxide production, was manifested when the Syk pathway was inhibited. C. albicans-induced cytokine production via Dectin-1 recognition is mediated by the Syk activation pathway. Indeed, specific Syk inhibition significantly suppressed the production of IL-12, IL-6, and TNF-alpha. Finally, we observed that Dectin-1 engagement was also involved in DC maturation and subsequent lymphocyte activation. Collectively, these findings identify Dectin-1 as a key receptor influencing critical biological functions of DC in response to C. albicans leading to T cells response alteration. These effects are largely, though not completely, mediated by Syk activation.
Microbiology Section, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy.
Franck
F
Skrzypek
Elio
E
Cenci
Donatella
D
Pietrella
Anna
A
Rachini
Francesco
F
Bistoni
Anna
A
Vecchiarelli
D002176:Candida albicans / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000276:immunology*; D037181:Lectins, C-Type; D008213:Lymphocyte Activation / Q000276:immunology; D008565:Membrane Proteins / Q000276:immunology*; D050296:Microbial Viability; D009419:Nerve Tissue Proteins / Q000276:immunology*; D009569:Nitric Oxide / Q000378:metabolism; D010587:Phagocytosis / Q000276:immunology; D011505:Protein-Tyrosine Kinases / Q000276:immunology*; D016897:Respiratory Burst / Q000276:immunology; D013481:Superoxides / Q000378:metabolism; D000072377:Syk Kinase; D000099181:Dectin-1
D047908:Intracellular Signaling Peptides and Proteins; D037181:Lectins, C-Type; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D009569:Nitric Oxide; D011505:Protein-Tyrosine Kinases; D013481:Superoxides; D000072377:Syk Kinase; D000099181:Dectin-1; C000606896:SYK protein, human