RRC ID 40081
Author Nakamura Y, Sato K, Yamamoto H, Matsumura K, Matsumoto I, Nomura T, Miyasaka T, Ishii K, Kanno E, Tachi M, Yamasaki S, Saijo S, Iwakura Y, Kawakami K.
Title Dectin-2 deficiency promotes Th2 response and mucin production in the lungs after pulmonary infection with Cryptococcus neoformans.
Journal Infect Immun
Abstract Dectin-2 is a C-type lectin receptor that recognizes high mannose polysaccharides. Cryptococcus neoformans, a yeast-form fungal pathogen, is rich in polysaccharides in its cell wall and capsule. In the present study, we analyzed the role of Dectin-2 in the host defense against C. neoformans infection. In Dectin-2 gene-disrupted (knockout) (Dectin-2KO) mice, the clearance of this fungus and the inflammatory response, as shown by histological analysis and accumulation of leukocytes in infected lungs, were comparable to those in wild-type (WT) mice. The production of type 2 helper T (Th2) cytokines in lungs was higher in Dectin-2KO mice than in WT mice after infection, whereas there was no difference in the levels of production of Th1, Th17, and proinflammatory cytokines between these mice. Mucin production was significantly increased in Dectin-2KO mice, and this increase was reversed by administration of anti-interleukin 4 (IL-4) monoclonal antibody (MAb). The levels of expression of β1-defensin, cathelicidin, surfactant protein A (Sp-A), and Sp-D in infected lungs were comparable between these mice. In in vitro experiments, IL-12p40 and tumor necrosis factor alpha (TNF-α) production and expression of CD86 and major histocompatibility complex (MHC) class II by bone marrow-derived dendritic cells and alveolar macrophages were completely abrogated in Dectin-2KO mice. Finally, the disrupted lysates of C. neoformans, but not of whole yeast cells, activated Dectin-2-triggered signaling in an assay with nuclear factor of activated T cells (NFAT)-green fluorescent protein (GFP) reporter cells expressing this receptor. These results suggest that Dectin-2 may oppose the Th2 response and IL-4-dependent mucin production in the lungs after infection with C. neoformans, and it may not be required for the production of Th1, Th17, and proinflammatory cytokines or for clearance of this fungal pathogen.
Volume 83(2)
Pages 671-81
Published 2015-2-1
DOI 10.1128/IAI.02835-14
PII IAI.02835-14
PMID 25422263
PMC PMC4294247
MeSH Animals Antibodies, Monoclonal / immunology Antimicrobial Cationic Peptides / biosynthesis B7-2 Antigen / biosynthesis Cathelicidins Cells, Cultured Cryptococcosis / immunology* Cryptococcus neoformans / immunology* Defensins / biosynthesis Dendritic Cells / immunology Female Green Fluorescent Proteins / genetics Histocompatibility Antigens Class II / biosynthesis Inflammation / genetics Inflammation / immunology Interleukin-12 Subunit p40 / biosynthesis Interleukin-4 / immunology Lectins, C-Type / genetics* Lectins, C-Type / immunology Lung / microbiology Lung / pathology Lung Diseases, Fungal / immunology Macrophages, Alveolar / immunology Male Mice Mice, Inbred C57BL Mice, Knockout Mucins / biosynthesis Pulmonary Surfactant-Associated Protein A / biosynthesis Pulmonary Surfactant-Associated Protein D / biosynthesis Th1 Cells / immunology Th17 Cells / immunology Th2 Cells / immunology* Tumor Necrosis Factor-alpha / biosynthesis
IF 3.201
Times Cited 32
Pathogenic microorganisms