CD103+ Conventional Dendritic Cells are Critical for TLR-dependent Host Defense against an Endemic Fungal Pathogen. Mus musculus

Innate immune cells shape the host response to microbial pathogens. Here we studied the role of TLR7/9 in dendritic cell (DC) responses to Histoplasma capsulatum, an intracellular fungal pathogen of humans. Whereas macrophages succumbed to Histoplasma infection, TLR7/9 were critical for DCs to produce Type I interferons (IFN-I), restrict fungal growth, and survive fungal infection. In the mouse model of infection, optimal IFN-I and IFN gamma production, host survival, and restriction of cerebral fungal burden were also dependent on TLR7/9. Interestingly, CD103+ conventional DCs were the major producer of IFN-I in the lungs of infected mice, revealing a previously unknown role for these cells and uncovering their pivotal function in modulating the host immune response to endemic fungi. Overall design: In 6-well tissue culture treated dishes, 1 x 10 6 BMDCs or BMMs were subjected to either mock infection, infection with UV-treated Histoplasma, or infection with live Histoplasma yeasts at an MOI of 4. UV-treated (UVT) yeasts were prepared by subjecting G217B to UV light (UV Stratalinker 1800) for 1 hour; these yeasts failed to generate colonies when plated on HMM agarose.