title: CX3CR1 is dispensable for control of mucosal Candida albicans infections in mice and humans.
abstract: Candida albicans is part of the normal commensal microbiota of mucosal surfaces in a large percentage of the human population. However, perturbations of the host's immune response or bacterial microbiota have been shown to predispose individuals to the development of opportunistic Candida infections. It was recently discovered that a defect in the chemokine receptor CX3CR1 increases susceptibility of mice and humans to systemic candidiasis. However, whether CX3CR1 confers protection against mucosal C. albicans infection has not been investigated. Using two different mouse models, we found that Cx3cr1 is dispensable for the induction of interleukin 17A (IL-17A), IL-22, and IL-23 in the tongue after infection, as well as for the clearance of mucosal candidiasis from the tongue or lower gastrointestinal (GI) tract colonization. Furthermore, the dysfunctional human CX3CR1 allele CX3CR1-M280 was not associated with development of recurrent vulvovaginal candidiasis (RVVC) in women. Taken together, these data indicate that CX3CR1 is not essential for protection of the host against mucosal candidiasis, underscoring the dependence on different mammalian immune factors for control of mucosal versus systemic Candida infections.
authors.affiliation: Fungal Pathogenesis Unit, Laboratory of Clinical Infectious Disease, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Break
authors.affiliation: Radboud University Medical Center and Radboud Center for Infectious Diseases (RCI), Nijmegen, The Netherlands.
authors.forename: Martin
authors.initials: M
authors.lastname: Jaeger
authors.affiliation: Division of Infectious Diseases, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California, USA.
authors.forename: Norma V
authors.initials: NV
authors.lastname: Solis
authors.affiliation: Division of Infectious Diseases, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California, USA The David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
authors.forename: Scott G
authors.initials: SG
authors.lastname: Filler
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Rodriguez
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Jean K
authors.initials: JK
authors.lastname: Lim
authors.affiliation: Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland, USA.
authors.forename: Chyi-Chia Richard
authors.initials: CC
authors.lastname: Lee
authors.affiliation: Department of Infectious Diseases, Wayne State University School of Medicine, Detroit, Michigan, USA.
authors.forename: Jack D
authors.initials: JD
authors.lastname: Sobel
authors.affiliation: Radboud University Medical Center and Radboud Center for Infectious Diseases (RCI), Nijmegen, The Netherlands.
authors.forename: Mihai G
authors.initials: MG
authors.lastname: Netea
authors.affiliation: Fungal Pathogenesis Unit, Laboratory of Clinical Infectious Disease, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA lionakism@niaid.nih.gov.
authors.forename: Michail S
authors.initials: MS
authors.lastname: Lionakis
mesh_terms: D000483:Alleles; D000818:Animals; D000073883:CX3C Chemokine Receptor 1; D002176:Candida albicans / Q000276:immunology*; D002177:Candidiasis / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D002181:Candidiasis, Vulvovaginal / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D004195:Disease Models, Animal; D005260:Female; D041981:Gastrointestinal Tract / Q000276:immunology / Q000382:microbiology; D015870:Gene Expression; D054884:Host-Pathogen Interactions; D006801:Humans; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology; D053759:Interleukin-23 / Q000235:genetics / Q000276:immunology; D007378:Interleukins / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009894:Opportunistic Infections / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D019707:Receptors, Chemokine / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D014059:Tongue / Q000276:immunology / Q000382:microbiology; D014621:Vagina / Q000276:immunology / Q000382:microbiology; D000097043:Interleukin-22
chemical_list: D000073883:CX3C Chemokine Receptor 1; D020381:Interleukin-17; D053759:Interleukin-23; D007378:Interleukins; D019707:Receptors, Chemokine; D000097043:Interleukin-22; C095235:CX3CR1 protein, human; C508717:IL17A protein, human