Cryptococcosis is an opportunistic disease caused by the fungus Cryptococcus neoformans and Cryptococcus gattii. It starts as a pulmonary infection that can spread to other organs, such as the brain, leading to the most serious occurrence of the disease, meningoencephalitis. The humoral response has already been described in limiting the progression of cryptococcosis where the B-1 cell seems to be responsible for producing natural IgM antibodies, crucial for combating fungal infections. The role of the B-1 cell in C. neoformans infection has been initially described, however the role of the humoral response of B-1 cells has not yet been evaluated during C. gattii infections. In the present study we tried to unravel this issue using XID mice, a murine model deficient in the Btk protein which compromises the development of B-1 lymphocytes. We use the XID mice compared to BALB/c mice that are sufficient for the B-1 population during C. gattii infection. Our model of chronic lung infection revealed that XID mice, unlike the sufficient group of B-1, had early mortality with significant weight loss, in addition to reduced levels of IgM and IgG specific to GXM isolated from the capsule of C. neoformans. In addition to this, we observed an increased fungal load in the blood and in the brain. We described an increase in the capsular size of C. gattii and the predominant presence of cytokines with a Th2 profile was also observed in these animals. Thus, the present study strongly points to a higher susceptibility of the XID mouse to C. gattii, which suggests that the presence of B-1 cells and anti-GXM antibodies is fundamental during the control of infection by C. gattii.
The diagnosis of Invasive Fungal Disease (IFD) is difficult because the sensitivity of conventional culture and cytology methods for the detection of Aspergillus is poor, and because serological methods exhibit cross-reactivity with environmental fungi. Fungal polysaccharides are of particular interest in the serologic diagnosis of IFD, especially galactomannan (GM) and glucan, which have been recognized as useful tools for the diagnosis of fungal infections. Further investigation into polysaccharide antibody cross-reactivity is important in improving diagnostic tests. Our aim was to verify the production of antibodies against fungal antigens in mice immunized with exopolysaccharides (EPS) obtained from three fungal species (Aspergillus terreus, Paecilomyces variotii and Curvularia brachyspora). ELISA assays were performed to evaluate homologous and heterologous reactions and showed anti-polysaccharide antibodies production. EPS from A. terreus was immunogenic enough to immunize the animal and lead to antibody production against this EPS. In addition, no cross-reactivity was observed with EPS obtained from P. variotii and C. brachyspora. The EPS from P. variotii did not exhibit good immunogenicity, whereas EPS from C. brachyspora showed good immunogenicity, and heterologous reactions were detected on the ELISA assays performed using the EPS from this species. The results indicate that immunization can occur for environmental fungal polysaccharides, generating antibodies may be interfere in serological diagnosis that are based on detection of fungal polysaccharides, mainly glucans and galactomannans.
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