Open AccessComplex Roles of Annexin A2 in Host Blood–Brain Barrier Invasion by Cryptococcus neoformans
Author(s) -
Fang Wei,
Fa ZhenZong,
Xie Qun,
Wang GuiZhen,
Yi Jiu,
Zhang Chao,
Meng GuangXun,
Gu JuLin,
Liao WanQing
Publication year - 2017
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.12673
Subject(s) - transcytosis , cryptococcus neoformans , biology , annexin a2 , microbiology and biotechnology , endocytosis , immunology , annexin , cell , flow cytometry , biochemistry
Summary Introduction Fungal transversal across the brain microvascular endothelial cells ( BMEC s) is the essential step for the development of cryptococcal meningoencephalitis. Annexin A2 (AnxA2) is an important signaling protein involved in several intracellular processes such as membrane trafficking, endocytosis, and exocytosis. Aim To investigate the roles and mechanism of AnxA2 during cryptococcal transversal of BMEC s. Results Cryptococcus neoformans infection initiated upregulation of AnxA2 in mouse BMEC s. Blockade with anti‐AnxA2 antibody led to a reduction in fungal transcytosis activity but no change in its adhesion efficiency. Intriguingly, AnxA2 depletion caused a significant increase in fungal association activity but had no effect on their transcytosis. AnxA2 suppression resulted in marked reduction in its partner protein S100A10, and S100A10 suppression in BMEC s significantly reduced the cryptococcal transcytosis efficiency. Furthermore, AnxA2 dephosphorylation at Tyr23 and dephosphorylation of downstream cofilin were required for cryptococcal transversal of BMEC s, both of which might be primarily involved in the association of C. neoformans with host cells. Conclusions Our work indicated that AnxA2 played complex roles in traversal of C. neoformans across host BMEC s, which might be dependent on downstream cofilin to inhibit fungal adhesion but rely on its partner S100A10 to promote cryptococcal transcytosis.