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Sci Rep. 2018 Feb 8;8(1):2681. doi: 10.1038/s41598-018-21039-z.

Identification of T helper (Th)1- and Th2-associated antigens of Cryptococcus neoformans in a murine model of pulmonary infection.

Author information

1
Institute of Immunology/Molecular Pathogenesis, Centre for Biotechnology and Biomedicine, College of Veterinary Medicine, University of Leipzig, Leipzig, Germany.
2
Group of Microbiology, National Institute of Health, Bogota, Colombia.
3
School of Medicine and Health Sciences, Universidad del Rosario, Bogota, Colombia.
4
Department of Molecular Systems Biology, Helmholtz-Centre for Environmental Research, Leipzig, Germany.
5
Research Group Microbial Immunology, Leibniz Institute for Natural Product Research and Infection Biology, Hans-Knöll-Institute (HKI), Jena, Germany.
6
International Centre for Genetic Engineering & Biotechnology (ICGEB), Cape Town component, South Africa and University of Cape Town, Division Immunology, Institute of Infectious Diseases and Molecular Medicine (IDM) & South African Medical Research Council (SAMRC), Cape Town, South Africa.
7
Institute of Biochemistry, Faculty of Biosciences, Pharmacy and Psychology, University of Leipzig, Leipzig, Germany.
8
Institute of Immunology/Molecular Pathogenesis, Centre for Biotechnology and Biomedicine, College of Veterinary Medicine, University of Leipzig, Leipzig, Germany. alber@vetmed.uni-leipzig.de.

Abstract

Cryptococcosis, caused by Cryptococcus neoformans, has been demonstrated to be controlled by T helper (Th)1 cells while Th2 cells are associated with fungal growth and dissemination. Although cryptococcal immunoreactive protein antigens were previously identified, their association with Th1 or Th2 immune responses was not provided. In mice, Th1-dependent IFN-γ induces the production of IgG2a, whereas the Th2 cytokine IL-4 stimulates the expression of IgG1 rendering each isotype an indicator of the underlying Th cell response. Therefore, we performed an immunoproteomic study that distinguishes Th1- and Th2-associated antigens by their reactivity with Th1-dependent IgG2a or Th2-dependent IgG1 antibodies in sera from C. neoformans-infected wild-type mice. We additionally analysed sera from Th2-prone IL-12-deficient and Th1-prone IL-4Rα-deficient mice extending the results found in wild-type mice. In total, ten, four, and three protein antigens associated with IgG1, IgG2a, or both isotypes, respectively, were identified. Th2-associated antigens represent promising candidates for development of immunotherapy regimens, whereas Th1-associated antigens may serve as candidates for vaccine development. In conclusion, this study points to intrinsic immunomodulatory effects of fungal antigens on the process of Th cell differentiation based on the identification of cryptococcal protein antigens specifically associated with Th1 or Th2 responses throughout mice of different genotypes.

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