Antifungal Activity of Plasmacytoid Dendritic Cells against Cryptococcus neoformans In Vitro Requires Expression of Dectin-3 (CLEC4D) and Reactive Oxygen Species.
Conventional dendritic cells (cDCs) are critical for protection against pulmonary infection with the opportunistic fungal pathogen Cryptococcus neoformans; however, the role of plasmacytoid dendritic cells (pDCs) is unknown. We show for the first time that murine pDCs have direct activity against C. neoformans via reactive oxygen species (ROS), a mechanism different from that employed to control Aspergillus fumigatus infections. The anticryptococcal activity of murine pDCs is independent of opsonization but appears to require the C-type lectin receptor Dectin-3, a receptor not previously evaluated during cryptococcal infections. Human pDCs can also inhibit cryptococcal growth by a mechanism similar to that of murine pDCs. Experimental pulmonary infection of mice with a C. neoformans strain that induces protective immunity demonstrated that recruitment of pDCs to the lungs is CXCR3 dependent. Taken together, our results show that pDCs inhibit C. neoformans growth in vitro via the production of ROS and that Dectin-3 is required for optimal growth-inhibitory activity.
Department of Biology, The University of Texas at San Antonio, San Antonio, Texas, USA South Texas Center for Emerging Infectious Diseases, The University of Texas at San Antonio, San Antonio, Texas, USA.
Camaron R
CR
Hole
Department of Biology, The University of Texas at San Antonio, San Antonio, Texas, USA South Texas Center for Emerging Infectious Diseases, The University of Texas at San Antonio, San Antonio, Texas, USA.
Chrissy M
CM
Leopold Wager
Department of Biology, The University of Texas at San Antonio, San Antonio, Texas, USA South Texas Center for Emerging Infectious Diseases, The University of Texas at San Antonio, San Antonio, Texas, USA.
Andrew S
AS
Mendiola
Department of Biology, The University of Texas at San Antonio, San Antonio, Texas, USA South Texas Center for Emerging Infectious Diseases, The University of Texas at San Antonio, San Antonio, Texas, USA.
Karen L
KL
Wozniak
Department of Biology, The University of Texas at San Antonio, San Antonio, Texas, USA South Texas Center for Emerging Infectious Diseases, The University of Texas at San Antonio, San Antonio, Texas, USA.
Althea
A
Campuzano
Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA Cancer Biology Program, The University of Texas Graduate School of Biomedical Sciences, Houston, Texas, USA.
Xin
X
Lin
Department of Biology, The University of Texas at San Antonio, San Antonio, Texas, USA South Texas Center for Emerging Infectious Diseases, The University of Texas at San Antonio, San Antonio, Texas, USA floyd.wormley@utsa.edu.
Floyd L
FL
Wormley
D000818:Animals; D000935:Antifungal Agents / Q000276:immunology* / Q000378:metabolism*; D001228:Aspergillosis / Q000276:immunology; D001232:Aspergillus fumigatus / Q000276:immunology; D003453:Cryptococcosis / Q000276:immunology; D003455:Cryptococcus neoformans / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism*; D005260:Female; D006801:Humans; D037181:Lectins, C-Type / Q000378:metabolism*; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D017382:Reactive Oxygen Species / Q000378:metabolism*
D000935:Antifungal Agents; D037181:Lectins, C-Type; D017382:Reactive Oxygen Species