title: Host-microbe interactions in stem cell transplantation: recognizing Candida in infection and inflammation.
abstract: Host-pathogen interactions at epithelial barriers play an important role in health and disease. This also applies to the clinical setting of stem cell transplantation (SCT) in which deregulated sensing of microbes and their cell wall components by pattern recognition receptors (PRRs) can contribute to inflammatory and infectious complications. The role of Candida species herein has recently been rediscovered since a 'loss-of-function' Y238X polymorphism in dectin-1, a C-type lectin receptor recognizing the β-1,3-glucan motif of Candida, resulted in diminished membrane expression and lower cytokine responses upon β-1,3-glucan recognition, and was associated with increased Candida colonization of SCT recipients, rendering them at risk for candidaemia. In addition, Candida colonization was associated with an increased incidence of acute graft-versus-host disease (GvHD), but only in those individuals with the wild-type dectin-1 allele. The Th17 mediated immune responses might provide a common link in these processes, as they have recently been implicated in anti-Candida immunity as well as the pathogenesis of GvHD. These new insights suggest that immunogenetics could contribute to a more individualized risk-based strategy for managing SCT recipients, for example concerning antifungal prophylaxis. In addition, modulating host-pathogen interactions by selectively modulating PRR activity could be exploited in SCT to achieve better outcomes.
authors.affiliation: Department of Hematology, Radboud University, Nijmegen Medical Center, the Netherlands. w.vandervelden@hemat.umcn.nl
authors.forename: Walter J F M
authors.initials: WJ
authors.lastname: van der Velden
authors.forename: Theo S
authors.initials: TS
authors.lastname: Plantinga
authors.forename: J Peter
authors.initials: JP
authors.lastname: Donnelly
authors.forename: Bart-Jan
authors.initials: BJ
authors.lastname: Kullberg
authors.forename: Nicole M A
authors.initials: NM
authors.lastname: Blijlevens
authors.forename: Mihai G
authors.initials: MG
authors.lastname: Netea
mesh_terms: D002175:Candida / Q000254:growth & development / Q000276:immunology / Q000378:metabolism* / Q000472:pathogenicity; D002177:Candidiasis / Q000453:epidemiology / Q000276:immunology / Q000382:microbiology*; D002462:Cell Membrane / Q000378:metabolism*; D006086:Graft vs Host Disease / Q000453:epidemiology* / Q000276:immunology / Q000503:physiopathology; D054884:Host-Pathogen Interactions; D006801:Humans; D015994:Incidence; D007249:Inflammation / Q000453:epidemiology / Q000276:immunology / Q000382:microbiology* / Q000503:physiopathology; D037181:Lectins, C-Type; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide; D051192:Receptors, Pattern Recognition / Q000378:metabolism; D033581:Stem Cell Transplantation / Q000009:adverse effects*; D058504:Th17 Cells / Q000276:immunology; D000099181:Dectin-1
chemical_list: D037181:Lectins, C-Type; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D051192:Receptors, Pattern Recognition; D000099181:Dectin-1