4.6 Article

Pulmonary Conventional Type 1 Langerin-Expressing Dendritic Cells Play a Role in Impairing Early Protective Immune Response against Cryptococcus neoformans Infection in Mice

Journal

JOURNAL OF FUNGI
Volume 8, Issue 8, Pages -

Publisher

MDPI
DOI: 10.3390/jof8080792

Keywords

cryptococcosis; lung dendritic cells; DC1

Funding

  1. Ministerio de Ciencia y Tecnologia de la Provincia de Cordoba, Argentina
  2. Secretaria de Ciencia y Tecnologia, Universidad Nacional de Cordoba
  3. Agencia Nacional de Promocion Cientifica y Tecnologica, Fondo para la Investigacion Cientifica y Tecnologica [1425, 1349]
  4. CONICET [11220150100260]

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This study provides evidence for the function of lung dendritic cells during pulmonary infection. The results suggest that LangDC1 cells impair immune response, affecting the clearance of C. neoformans in the early stage of cryptococcosis.
Lung dendritic cells (DC) are powerful antigen-presenting cells constituted by various subpopulations that differ in terms of their function and origin and differentially regulate cell-mediated antifungal immunity. The lung is the primary target organ of Cryptococcus neoformans and C. gattii infections, which makes it essential in the establishment of the first line of anti-cryptococcal defense. However, the lung-specific dynamics and function of DC subsets are poorly understood in cryptococcosis. In this study, we provide evidence for the in vivo function of a conventional langerin-expressing DC1 dendritic cell (LangDC1) population during the first week of intratracheal C. neoformans infection in mice. By using conditional depletion of LangDC1 after diphtheria toxin treatment of LangDTREGFP mice, we demonstrate that these animals better control the fungal infection and produce type 1 and 17 cytokines in the context of a type 2 immune response, favoring a predominance of iNOS over arginase-1 expression by pulmonary cells. Our results suggest that LangDC1 cells play a role in impairing immune response for the clearance of C. neoformans in the early stage of pulmonary infection.

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