This report describes a case of Cryptococcus gattii VGIIb infection of the pulmonary and central nervous systems in an immunocompetent Japanese man with a travel history, and it hypothesizes the place where he was infected with C. gattii using the genotype information.

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[in Japanese]

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Cryptococcus neoformans is a medically important opportunistic fungal pathogen with a polysaccharide capsule surrounding the yeast-like cells. In hosts with impaired cell-mediated immunity such as AIDS, uncontrolled infection causes life-threatening meningoencephalitis. In immunocompetent individuals, the host immune response usually limits the growth of the fungal pathogen at the primary infected site, where it may persist, without completely eradicated, in a latent state because of its ability to escape from killing by macrophages. Th1 response in adaptive immunity is essential for the host defense to cryptococcal infection, in which interferon (IFN)-γ polarizes innate macrophages into fungicidal M1 macrophages. Recently, we found that caspase recruitment domain family member (CARD9), an adaptor protein in a signal transduction triggered by C-type lectin receptors, plays a key role in the early production of IFN-γ at the site of infection by recruiting NK cells and CD4⁺ and CD8⁺ memory-phenotype T cells. We also found that IL-4 produced by Th2 cells stimulates broncoepithelial cells to secrete mucin, which may lead to promotion in the mucociliary clearance of C. neoformans. Here, we summarize the up-to-date findings in the host defense mechanism to this infection with focusing on our recent data.

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Candida species are one major causal microorganism of hospital acquired bloodstream infections associated with high mortality. Phagocytes like neutrophils in innate immunity and CD4 T cells in acquired immunity have a major role in host defense immune response. It has been recently found that a type of innate-like lymphocyte called NKT cells respond against various organisms but its role in candidal infection remained unknown. Thus, we analyzed the role of NKT cells in the immune response against systemic candidiasis using mice deficient of NKT cells. In vivo studies revealed that invariant NKT cells play a limited role for controlling systemic candidal infection. On the other hand, studies looking at the role of glycolipid-activated NKT cells during candidal infection revealed that candida-infected mice injected with glycolipid had shorter survival period and greater number of fungal colonies in the kidney accompanied with reduced number of neutrophils in the blood and bone marrow. Surprisingly, glycolipid-mediated exacerbation of candidal infection was absent in IFNγ deficient mice. Co-infection of candida with intestinal commensals caused exacerbated infection in which IFNγ played a critical role in impairing fungal elimination. These results suggest that the excessive IFNγ released from candida and bacterial co-infection is a critical factor in worsening candidal infection.

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The effect of S-PT84, a heat-killed preparation of Lactobacillus pentosus on growth of Candida albicans was examined in vitro and in vivo. The mycelial growth was effectively inhibited by S-PT84 and seemed to bind to the hyphae. We assessed the potential of S-PT84 for treatment of oral and gastric candidiasis using a murine model. When 2 mg of S-PT84 was administered three times into the oral cavity of orally Candida infected mice, the score of lesions on the tongue was improved on day 2. When 50μl and 200μl of S-PT84 (10 mg/ml) were administered three times into the oral cavity (0.5 mg × 3) and the stomach (2 mg × 3) of the same mouse model, the number of viable Candida cells in the stomach was reduced significantly on day 2.
These findings suggest the possibility that S-PT84 has potential as a food ingredient supporting anti-Candida treatment, especially for Candida infection in the gastrointestinal tract.

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