Limited Role of Mincle in the Host Defense against Infection with Cryptococcus deneoformans

Abstract

Cryptococcus deneoformans is an opportunistic fungal pathogen that frequently causes fatal meningoencephalitis in patients with impaired cell-mediated immune responses such as AIDS. Caspase-associated recruitment domain 9 (CARD9) plays a critical role in the host defense against cryptococcal infection, suggesting the involvement of one or more C-type lectin receptors (CLRs). In the present study, we analyzed the role of macrophage-inducible C-type lectin (Mincle), one of the CLRs, in the host defense against C. deneoformans infection. Mincle expression in the lungs of wild-type (WT) mice was increased in the early stage of cryptococcal infection in a CARD9-dependent manner. In Mincle gene-disrupted (Mincle KO) mice, the clearance of this fungus, pathological findings, Th1/Th2 response, and antimicrobial peptide production in the infected lungs were nearly comparable to those in WT mice. However, the production of IL-22, TNF-α, and IL-6 and the expression of AhR were significantly decreased in the lungs of Mincle KO mice compared to in WT mice. In in vitro experiments, TNF-α production by bone marrow-derived dendritic cells was significantly decreased in Mincle KO mice. In addition, the disrupted lysates of C. deneoformans, but not of whole yeast cells, activated Mincle-triggered signaling in an assay with a nuclear factor of activated T cells (NFAT)-green fluorescent protein (GFP) reporter cells expressing this receptor. These results suggest that Mincle may be involved in the production of Th22-related cytokines at the early stage of cryptococcal infection, although its role may be limited in the host defense against infection with C. deneoformans.

Contribution of Invariant Natural Killer T Cells to the Clearance of Pseudomonas aeruginosa from Skin Wounds

“…These observations suggest that the ability of APCs to produce IL-1β and IL-23 may not differ between WT and Jα18KO mice, and that IL-17A and IL-22 production may be caused by the activated iNKT cells. IL-17A and IL-22 are known to contribute to the epithelial barrier function against bacterial infection through inducing the production of AMPs, including β-defensins and S100 proteins [ 11 , 39 ]. Consistent with the results of previous studies, we found that AMP production was significantly reduced in Jα18KO mice compared with that of WT mice, which was accompanied by the reduced production of IL-17A and IL-22.…”

PAMPs and Host Immune Response in Cryptococcal Infection

“…It has been reported that GlcCer immunization protected the host from C. neoformans infection 57) . In our previous study, Mincle, a CLR, recognized fungal β -GlcCer and induced the Th22 immune response after infection with C. deneoformans 58) . Nucleic acids of pathogens induce an inflammatory response.…”

Deficiency of lung-specific claudin-18 leads to aggravated infection with Cryptococcus deneoformans through dysregulation of the microenvironment in lungs

“…Isotype-matched IgG was used for control staining. The stained cells were analyzed using a BD FACS Canto II flow cytometer (BD Bioscience) as previously described 11 , 31 – 33 .…”