Batf3-dependent CD103(+) dendritic cell accumulation is dispensable for mucosal and systemic antifungal host defense

Virulence. 2016 Oct 2;7(7):826-35. doi: 10.1080/21505594.2016.1186324. Epub 2016 May 18.

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.

Keywords: Batf3; CD103; IL-12; dendritic cells; fungal infection; innate immunity; oropharyngeal candidiasis; systemic candidiasis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Antigens, CD / analysis*
  • Basic-Leucine Zipper Transcription Factors / genetics
  • Basic-Leucine Zipper Transcription Factors / immunology*
  • Candidiasis, Invasive / immunology*
  • Candidiasis, Invasive / microbiology
  • Candidiasis, Oral / immunology*
  • Candidiasis, Oral / microbiology
  • Cell Proliferation
  • Dendritic Cells / immunology*
  • Dendritic Cells / physiology
  • Immunity, Innate
  • Integrin alpha Chains / analysis*
  • Integrin alpha Chains / deficiency
  • Interleukin-12 / biosynthesis
  • Interleukin-12 / immunology
  • Kidney / immunology
  • Mice
  • Mice, Inbred C57BL
  • Repressor Proteins / genetics
  • Repressor Proteins / immunology*
  • Tongue / immunology

Substances

  • Antigens, CD
  • Basic-Leucine Zipper Transcription Factors
  • Integrin alpha Chains
  • Repressor Proteins
  • SNFT protein, mouse
  • alpha E integrins
  • Interleukin-12