title: Batf3-dependent CD103(+) dendritic cell accumulation is dispensable for mucosal and systemic antifungal host defense.
abstract: Dendritic cells (DCs) are critical for defense against a variety of pathogens and the formation of adaptive immune responses. The transcription factor Batf3 is critical for the development of CD103(+)CD11b(-) DCs, which promote IL-12-dependent protective immunity during viral and parasitic infections, dampen Th2 immunity during helminthic infection, and exert detrimental effects during bacterial infection. Whether CD103(+) DCs modulate immunity during systemic or mucosal fungal disease remains unknown. Herein, we report that Batf3 is critical for accumulation of CD103(+) DCs in the kidney and tongue at steady state, for their expansion during systemic and oropharyngeal candidiasis, and for tissue-specific production of IL-12 in kidney but not tongue during systemic and oropharyngeal candidiasis, respectively. Importantly, deficiency of CD103(+) DCs does not impair survival or fungal clearance during systemic or oropharyngeal candidiasis, indicating that Batf3-dependent CD103(+) DC accumulation mediates pathogen- and tissue-specific immune effects.
authors.affiliation: a Fungal Pathogenesis Unit, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda , MD , USA.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Break
authors.affiliation: b Department of Microbiology , Icahn School of Medicine at Mount Sinai , New York , NY , USA.
authors.forename: Kevin W
authors.initials: KW
authors.lastname: Hoffman
authors.affiliation: a Fungal Pathogenesis Unit, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda , MD , USA.
authors.forename: Muthulekha
authors.initials: M
authors.lastname: Swamydas
authors.affiliation: c Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health , Bethesda , MD , USA.
authors.forename: Chyi-Chia Richard
authors.initials: CC
authors.lastname: Lee
authors.affiliation: b Department of Microbiology , Icahn School of Medicine at Mount Sinai , New York , NY , USA.
authors.forename: Jean K
authors.initials: JK
authors.lastname: Lim
authors.affiliation: a Fungal Pathogenesis Unit, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda , MD , USA.
authors.forename: Michail S
authors.initials: MS
authors.lastname: Lionakis
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000032:analysis*; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics / Q000276:immunology*; D058365:Candidiasis, Invasive / Q000276:immunology* / Q000382:microbiology; D002180:Candidiasis, Oral / Q000276:immunology* / Q000382:microbiology; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000276:immunology* / Q000502:physiology; D007113:Immunity, Innate; D039001:Integrin alpha Chains / Q000032:analysis* / Q000172:deficiency; D018664:Interleukin-12 / Q000096:biosynthesis / Q000276:immunology; D007668:Kidney / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D012097:Repressor Proteins / Q000235:genetics / Q000276:immunology*; D014059:Tongue / Q000276:immunology
chemical_list: D015703:Antigens, CD; D050976:Basic-Leucine Zipper Transcription Factors; D039001:Integrin alpha Chains; D012097:Repressor Proteins; C533289:SNFT protein, mouse; C091367:alpha E integrins; D018664:Interleukin-12
keywords: Batf3; CD103; IL-12; dendritic cells; fungal infection; innate immunity; oropharyngeal candidiasis; systemic candidiasis