Candida Infection Biology – fungal armoury, battlefields ... - FINSysB

The role of pH-regulated antigen 1 of Candida albicans in
the interaction of the fungus with human neutrophils
Eliška Svobodová 1 , Josephine Losse 1 , Antje Heyken 2 , Bernhard Hube 2,4 ,
Peter F. Zipfel 3,4 and Mihály Józsi 1
1 Junior Research Group Cellular Immunobiology, 2 Department of Microbial Pathogenicity
Mechanisms and 3 Department of Infection Biology, Leibniz Institute for Natural Product
Research and Infection Biology - Hans Knöll Institute, Jena, Germany; 4 Friedrich Schiller
University, Jena, Germany
Candida albicans is an opportunistic human-pathogenic yeast and a leading cause
of life-threatening systemic fungal infections in immunocompromised individuals.
The virulence of the fungus is associated with its capability to filamentous growth.
The pH-regulated antigen 1 (Pra1) of C. albicans is a surface-associated and
secreted protein whose expression is upregulated in the hyphal form. Pra1 binds
to complement receptor 3 (CD11b/CD18) and can mediate adhesion to and
migration of human phagocytes. Here, we investigated the role of Pra1 in the
activation of human neutrophils. A C. albicans mutant strain lacking Pra1 (pra1 )
supported neutrophil migration to a lower extent than did the parental wild-type
strain. A Pra1-overexpressing C. albicans strain enhanced neutrophil migration and
adherence. While inactivated hyphae of the Pra1-overexpressing mutant enhanced
the production and release of reactive oxygen species, myeloperoxidase,
lactoferrin, and interleukin 8 by neutrophils, such responses were reduced when
stimulated with the pra1 strain. Pra1-overexpressing living hyphae also caused a
reduced neutrophil activation, indicating that fungal cells which express and release
more Pra1 can more efficiently inhibit the activation of these innate immune cells.
Fungal cells lacking Pra1 were more efficiently killed by neutrophils. The lack or the
overexpression of Pra1 did not significantly affect the generation of neutrophil
extracellular traps. In conclusion, surface-exposed Pra1 plays a role in the
recognition of C. albicans, especially hyphal cells, by human neutrophils and
enhances neutrophil antimicrobial responses. However, the fungus can counteract
some of these defense mechanisms likely by releasing Pra1.
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