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Insights into the mechanisms of protective immunity against Cryptococcus neoformans infection using a mouse model of pulmonary cryptococcosis

PLoS ONE, ISSN: 1932-6203, Vol: 4, Issue: 9, Page: e6854
2009
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Article Description

Cryptococcus neoformans is an opportunistic fungal pathogen that causes life-threatening pneumonia and meningoencephalitis in immune compromised individuals. Previous studies have shown that immunization of BALB/c mice with an IFN-γ-producing C. neoformans strain, H99γ, results in complete protection against a second pulmonary challenge with an otherwise lethal cryptococcal strain. The current study evaluated local anamnestic cell-mediated immune responses against pulmonary cryptococcosis in mice immunized with C. neoformans strain H99γ compared to mice immunized with heat-killed C. neoformans (HKC.n.). Mice immunized with C. neoformans strain H99γ had significantly reduced pulmonary fungal burden post-secondary challenge compared to mice immunized with HKC.n. Protection against pulmonary cryptococcosis was associated with increased pulmonary granulomatous formation and leukocyte infiltration followed by a rapid resolution of pulmonary inflammation, which protected the lungs from severe allergic bronchopulmonary mycosis (ABPM)-pathology that developed in the lungs of mice immunized with HKC.n. Pulmonary challenge of interleukin (IL)-4 receptor, IL-12p40, IL-12p35, IFN-γ, T cell and B cell deficient mice with C. neoformans strain H99γ demonstrated a requirement for Th1-type T cell-mediated immunity, but not B cell-mediated immunity, for the induction of H99γ-mediated protective immune responses against pulmonary C. neoformans infection. CD4 T cells, CD11c cells, and Gr-1 cells were increased in both proportion and absolute number in protected mice. In addition, significantly increased production of Th1-type/pro-inflammatory cytokines and chemokines, and conversely, reduced Th2-type cytokine production was observed in the lungs of protected mice. Interestingly, protection was not associated with increased production of cytokines IFN-γ or TNF-α in lungs of protected mice. In conclusion, immunization with C. neoformans strain H99γ results in the development of protective anti-cryptococcal immune responses that may be measured and subsequently used in the development of immune-based therapies to combat pulmonary cryptococcosis. © 2009 Wozniak et al.

Bibliographic Details

http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=70149108073&origin=inward; http://dx.doi.org/10.1371/journal.pone.0006854; http://www.ncbi.nlm.nih.gov/pubmed/19727388; https://dx.plos.org/10.1371/journal.pone.0006854.g002; http://dx.doi.org/10.1371/journal.pone.0006854.g002; https://dx.plos.org/10.1371/journal.pone.0006854.t002; http://dx.doi.org/10.1371/journal.pone.0006854.t002; https://dx.plos.org/10.1371/journal.pone.0006854.g001; http://dx.doi.org/10.1371/journal.pone.0006854.g001; https://dx.plos.org/10.1371/journal.pone.0006854.g006; http://dx.doi.org/10.1371/journal.pone.0006854.g006; https://dx.plos.org/10.1371/journal.pone.0006854.t001; http://dx.doi.org/10.1371/journal.pone.0006854.t001; https://dx.plos.org/10.1371/journal.pone.0006854.g007; http://dx.doi.org/10.1371/journal.pone.0006854.g007; https://dx.plos.org/10.1371/journal.pone.0006854.g005; http://dx.doi.org/10.1371/journal.pone.0006854.g005; https://dx.plos.org/10.1371/journal.pone.0006854.g004; http://dx.doi.org/10.1371/journal.pone.0006854.g004; https://dx.plos.org/10.1371/journal.pone.0006854.g003; http://dx.doi.org/10.1371/journal.pone.0006854.g003; https://dx.plos.org/10.1371/journal.pone.0006854; https://dx.doi.org/10.1371/journal.pone.0006854.g005; https://journals.plos.org/plosone/article/figure?id=10.1371/journal.pone.0006854.g005; https://dx.doi.org/10.1371/journal.pone.0006854.g007; https://journals.plos.org/plosone/article/figure?id=10.1371/journal.pone.0006854.g007; https://dx.doi.org/10.1371/journal.pone.0006854.g006; https://journals.plos.org/plosone/article/figure?id=10.1371/journal.pone.0006854.g006; https://dx.doi.org/10.1371/journal.pone.0006854.g004; https://journals.plos.org/plosone/article/figure?id=10.1371/journal.pone.0006854.g004; https://dx.doi.org/10.1371/journal.pone.0006854.g001; https://journals.plos.org/plosone/article/figure?id=10.1371/journal.pone.0006854.g001; https://dx.doi.org/10.1371/journal.pone.0006854.g003; https://journals.plos.org/plosone/article/figure?id=10.1371/journal.pone.0006854.g003; https://dx.doi.org/10.1371/journal.pone.0006854; https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0006854; https://dx.doi.org/10.1371/journal.pone.0006854.t001; https://journals.plos.org/plosone/article/figure?id=10.1371/journal.pone.0006854.t001; https://dx.doi.org/10.1371/journal.pone.0006854.t002; https://journals.plos.org/plosone/article/figure?id=10.1371/journal.pone.0006854.t002; https://dx.doi.org/10.1371/journal.pone.0006854.g002; https://journals.plos.org/plosone/article/figure?id=10.1371/journal.pone.0006854.g002; http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0006854; https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0006854&type=printable; http://www.plosone.org/article/metrics/info:doi/10.1371/journal.pone.0006854; http://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0006854&type=printable; http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0006854; http://dx.plos.org/10.1371/journal.pone.0006854.g001; http://dx.plos.org/10.1371/journal.pone.0006854.g003; http://dx.plos.org/10.1371/journal.pone.0006854.g006; http://dx.plos.org/10.1371/journal.pone.0006854; http://dx.plos.org/10.1371/journal.pone.0006854.t001; http://dx.plos.org/10.1371/journal.pone.0006854.g002; http://dx.plos.org/10.1371/journal.pone.0006854.t002; http://dx.plos.org/10.1371/journal.pone.0006854.g007; http://dx.plos.org/10.1371/journal.pone.0006854.g005; http://dx.plos.org/10.1371/journal.pone.0006854.g004

Karen L. Wozniak; Sailatha Ravi; Sandra Macias; Mattie L. Young; Michal A. Olszewski; Chad Steele; Floyd L. Wormley; Ping Wang

Public Library of Science (PLoS)

Multidisciplinary

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