PMID- 32376699
OWN - NLM
STAT- MEDLINE
DCOM- 20210715
LR  - 20210715
IS  - 2379-5042 (Electronic)
IS  - 2379-5042 (Linking)
VI  - 5
IP  - 3
DP  - 2020 May 6
TI  - Extracellular Vesicles from Aspergillus flavus Induce M1 Polarization In Vitro.
LID - 10.1128/mSphere.00190-20 [doi]
LID - e00190-20
AB  - Aspergillus flavus, a ubiquitous and saprophytic fungus, is the second most 
      common cause of aspergillosis worldwide. Several mechanisms contribute to the 
      establishment of the fungal infection. Extracellular vesicles (EVs) have been 
      described as "virulence factor delivery bags" in several fungal species, 
      demonstrating a crucial role during the infection. In this study, we evaluated 
      production of A. flavus EVs and their immunomodulatory functions. We verified 
      that A. flavus EVs induce macrophages to produce inflammatory mediators, such as 
      nitric oxide, tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), and 
      IL-1beta. Furthermore, the A. flavus EVs enhance phagocytosis and killing by 
      macrophages and induce M1 macrophage polarization in vitro In addition, a prior 
      inoculation of A. flavus EVs in Galleria mellonella larvae resulted in a 
      protective effect against the fungal infection. Our findings suggest that A. 
      flavus EVs are biologically active and affect the interaction between A. flavus 
      and host immune cells, priming the innate immune system to eliminate the fungal 
      infection. Collectively, our results suggest that A. flavus EVs play a crucial 
      role in aspergillosis.IMPORTANCE Immunocompromised patients are susceptible to 
      several fungal infections. The genus Aspergillus can cause increased morbidity 
      and mortality. Developing new therapies is essential to understand the fungal 
      biology mechanisms. Fungal EVs carry important virulence factors, thus playing 
      pivotal roles in fungal pathophysiology. No study to date has reported EV 
      production by Aspergillus flavus, a fungus considered to be the second most 
      common cause of aspergillosis and relevant food contaminator found worldwide. In 
      this study, we produced A. flavus EVs and evaluated the in vitro immunomodulatory 
      effects of EVs on bone marrow-derived macrophages (BMDMs) and in vivo effects in 
      a Galleria mellonella model.
CI  - Copyright (c) 2020 Brauer et al.
FAU - Brauer, Veronica S
AU  - Brauer VS
AD  - Department of Biochemistry and Immunology, Ribeirao Preto Medical School, 
      University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil.
FAU - Pessoni, Andre M
AU  - Pessoni AM
AD  - Department of Biochemistry and Immunology, Ribeirao Preto Medical School, 
      University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil.
FAU - Bitencourt, Tamires A
AU  - Bitencourt TA
AD  - Department of Biochemistry and Immunology, Ribeirao Preto Medical School, 
      University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil.
FAU - de Paula, Renato G
AU  - de Paula RG
AD  - Department of Physiological Sciences, Health Sciences Centre, Federal University 
      of Espirito Santo, Vitoria, Espirito Santo, Brazil.
FAU - de Oliveira Rocha, Liliana
AU  - de Oliveira Rocha L
AD  - Department of Food Science, Faculty of Food Engineering, Campinas State 
      University (UNICAMP), Campinas, Sao Paulo, Brazil.
FAU - Goldman, Gustavo H
AU  - Goldman GH
AUID- ORCID: 0000-0002-2986-350X
AD  - Faculdade de Ciencias Farmaceuticas de Ribeirao Preto, University of Sao Paulo, 
      Ribeirao Preto, Sao Paulo, Brazil.
FAU - Almeida, Fausto
AU  - Almeida F
AUID- ORCID: 0000-0002-3782-3698
AD  - Department of Biochemistry and Immunology, Ribeirao Preto Medical School, 
      University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil fbralmeida@usp.br.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200506
PL  - United States
TA  - mSphere
JT  - mSphere
JID - 101674533
SB  - IM
MH  - Animals
MH  - Aspergillosis/immunology/prevention & control
MH  - Aspergillus flavus/*immunology/pathogenicity
MH  - Cell Differentiation/*immunology
MH  - Cell Polarity
MH  - Extracellular Vesicles/*immunology
MH  - Immunomodulation
MH  - Larva/microbiology
MH  - Macrophages/immunology/*physiology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Moths/microbiology
PMC - PMC7203453
OTO - NOTNLM
OT  - Aspergillus flavus
OT  - Galleria mellonella
OT  - cytokine
OT  - extracellular vesicles
OT  - killing
OT  - macrophage
OT  - phagocytosis
OT  - polarization
EDAT- 2020/05/08 06:00
MHDA- 2021/07/16 06:00
PMCR- 2020/05/06
CRDT- 2020/05/08 06:00
PHST- 2020/05/08 06:00 [entrez]
PHST- 2020/05/08 06:00 [pubmed]
PHST- 2021/07/16 06:00 [medline]
PHST- 2020/05/06 00:00 [pmc-release]
AID - 5/3/e00190-20 [pii]
AID - mSphere00190-20 [pii]
AID - 10.1128/mSphere.00190-20 [doi]
PST - epublish
SO  - mSphere. 2020 May 6;5(3):e00190-20. doi: 10.1128/mSphere.00190-20.