@article{85511,
  keywords = {Animals, Humans, Membrane Proteins, Mice, Mice, Inbred C57BL, Female, Male, Cell Movement, T-Lymphocytes, Interferon Type I, Dendritic Cells, Antigens, CD8, Malaria, Mast Cells, Toll-Like Receptors, Uric Acid},
  author = {Pierre Guermonprez and Julie Helft and Carla Claser and Stephanie Deroubaix and Henry Karanje and Anna Gazumyan and Guillaume Darasse-J{\`e}ze and Stephanie Telerman and Ga{\"e}lle Breton and Heidi Schreiber and Natalia Frias-Staheli and Eva Billerbeck and Marcus Dorner and Charles Rice and Alexander Ploss and Florian Klein and Melissa Swiecki and Marco Colonna and Alice Kamphorst and Matthew Meredith and Rachel Niec and Constantin Takacs and Fadi Mikhail and Aswin Hari and David Bosque and Tom Eisenreich and Miriam Merad and Yan Shi and Florent Ginhoux and Laurent R{\'e}nia and Britta Urban and Michel Nussenzweig},
  title = {Inflammatory Flt3l is essential to mobilize dendritic cells and for T cell responses during Plasmodium infection.},
  abstract = {<p>Innate sensing mechanisms trigger a variety of humoral and cellular events that are essential to adaptive immune responses. Here we describe an innate sensing pathway triggered by Plasmodium infection that regulates dendritic cell homeostasis and adaptive immunity through Flt3 ligand (Flt3l) release. Plasmodium-induced Flt3l release in mice requires Toll-like receptor (TLR) activation and type I interferon (IFN) production. We found that type I IFN supports the upregulation of xanthine dehydrogenase, which metabolizes the xanthine accumulating in infected erythrocytes to uric acid. Uric acid crystals trigger mast cells to release soluble Flt3l from a pre-synthesized membrane-associated precursor. During infection, Flt3l preferentially stimulates expansion of the CD8-α(+) dendritic cell subset or its BDCA3(+) human dendritic cell equivalent and has a substantial impact on the magnitude of T cell activation, mostly in the CD8(+) compartment. Our findings highlight a new mechanism that regulates dendritic cell homeostasis and T cell responses to infection.</p>
},
  year = {2013},
  journal = {Nat Med},
  volume = {19},
  pages = {730-8},
  month = {06/2013},
  issn = {1546-170X},
  doi = {10.1038/nm.3197},
  language = {eng},
}