Annexin A2 depletion exacerbates the intracerebral microhemorrhage induced by acute rickettsia and Ebola virus infections.
Journal
PLoS neglected tropical diseases
ISSN: 1935-2735
Titre abrégé: PLoS Negl Trop Dis
Pays: United States
ID NLM: 101291488
Informations de publication
Date de publication:
07 2020
07 2020
Historique:
received:
23
11
2019
accepted:
02
06
2020
revised:
30
07
2020
pubmed:
21
7
2020
medline:
22
8
2020
entrez:
21
7
2020
Statut:
epublish
Résumé
Intracerebral microhemorrhages (CMHs) are small foci of hemorrhages in the cerebrum. Acute infections induced by some intracellular pathogens, including rickettsia, can result in CMHs. Annexin a2 (ANXA2) has been documented to play a functional role during intracellular bacterial adhesion. Here we report that ANXA2-knockout (KO) mice are more susceptible to CMHs in response to rickettsia and Ebola virus infections, suggesting an essential role of ANXA2 in protecting vascular integrity during these intracellular pathogen infections. Proteomic analysis via mass spectrometry of whole brain lysates and brain-derived endosomes from ANXA2-KO and wild-type (WT) mice post-infection with R. australis revealed that a variety of significant proteins were differentially expressed, and the follow-up function enrichment analysis had identified several relevant cell-cell junction functions. Immunohistology study confirmed that both infected WT and infected ANXA2-KO mice were subjected to adherens junctional protein (VE-cadherin) damages. However, key blood-brain barrier (BBB) components, tight junctional proteins ZO-1 and occludin, were disorganized in the brains from R. australis-infected ANXA2-KO mice, but not those of infected WT mice. Similar ANXA2-KO dependent CMHs and fragments of ZO-1 and occludin were also observed in Ebola virus-infected ANXA2-KO mice, but not found in infected WT mice. Overall, our study revealed a novel role of ANXA2 in the formation of CMHs during R. australis and Ebola virus infections; and the underlying mechanism is relevant to the role of ANXA2-regulated tight junctions and its role in stabilizing the BBB in these deadly infections.
Identifiants
pubmed: 32687500
doi: 10.1371/journal.pntd.0007960
pii: PNTD-D-19-01978
pmc: PMC7392349
doi:
Substances chimiques
Annexin A2
0
Antigens, CD
0
Cadherins
0
cadherin 5
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0007960Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM127596
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL142758
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI137785
Pays : United States
Organisme : NIAID NIH HHS
ID : R33 AI121644
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM111313
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI121012
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI132674
Pays : United States
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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