Differential IL-17 production and mannan recognition contribute to fungal pathogenicity and commensalism.
In this study, we present evidence of differential Th17 responses in human monocyte-derived dendritic cells exposed to the pathogenic Candida albicans or the nonpathogenic Saccharomyces cerevisiae. We use different forms of the microorganisms, cells, hyphae, and spores, as a toolbox to dissect the role of surface mannan in the fungal immune response. In contrast to the S. cerevisiae yeast cell-induced Th1 response, dendritic cells stimulated with spores or C. albicans hyphae induce cellular responses shifted toward Th17 differentiation. The differential recognition of specific mannan structures is the master regulator of the discrimination between harmful and harmless fungi. The switch between spores and yeast is crucial for the commensalism of S. cerevisiae and depends on the use of a different receptor repertoire. Understanding the role of cell wall recognition during infection might lead to understanding the boundaries between safety and pathogenicity.
Department of Preclinic and Clinic Pharmacology, University of Firenze, Firenze, Italy.
Lisa
L
Rizzetto
Mirela
M
Kuka
Carlotta
C
De Filippo
Alessandra
A
Cambi
Mihai G
MG
Netea
Luca
L
Beltrame
Giorgio
G
Napolitani
Maria Gabriella
MG
Torcia
Ugo
U
D'Oro
Duccio
D
Cavalieri
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D002176:Candida albicans / Q000254:growth & development / Q000276:immunology* / Q000378:metabolism / Q000472:pathogenicity*; D002236:Carbohydrate Conformation; D002454:Cell Differentiation / Q000276:immunology; D002473:Cell Wall / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D006801:Humans; D025301:Hyphae / Q000254:growth & development / Q000276:immunology / Q000472:pathogenicity; D018664:Interleukin-12 / Q000096:biosynthesis; D020381:Interleukin-17 / Q000096:biosynthesis* / Q000502:physiology; D008351:Mannans / Q000276:immunology / Q000378:metabolism*; D009000:Monocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D012441:Saccharomyces cerevisiae / Q000254:growth & development / Q000276:immunology*; D013172:Spores, Fungal / Q000254:growth & development / Q000276:immunology / Q000472:pathogenicity; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000382:microbiology
D020381:Interleukin-17; D008351:Mannans; D018664:Interleukin-12