PMID- 33173103
OWN - NLM
STAT- MEDLINE
DCOM- 20210322
LR  - 20210322
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 10
IP  - 1
DP  - 2020 Nov 10
TI  - Paracoccidioides brasiliensis downmodulates alpha3 integrin levels in human lung 
      epithelial cells in a TLR2-dependent manner.
PG  - 19483
LID - 10.1038/s41598-020-76557-6 [doi]
LID - 19483
AB  - Paracoccidioidomycosis (PCM) is the most prevalent systemic mycosis in Latin 
      America and may be caused by the species Paracoccidioides brasiliensis. In the 
      lungs, this fungus interacts with epithelial cells, activating host cell 
      signalling pathways, resulting in the production of inflammatory mediators. This 
      event may be initiated through the activation of Pattern-Recognition Receptors 
      such as Toll-like Receptors (TLRs). By interacting with cell wall components, 
      TLR2 is frequently related to fungal infections. In this work, we show that, 
      after 24 h post-infection with P. brasiliensis, A549 lung epithelial cells 
      presented higher TLR2 levels, which is important for IL-8 secretion. Besides, 
      integrins may also participate in pathogen recognition by host cells. We verified 
      that P. brasiliensis increased alpha3 integrin levels in A549 cells after 5 h of 
      infection and promoted interaction between this receptor and TLR2. However, after 
      24 h, surprisingly, we verified a decrease of alpha3 integrin levels, which was 
      dependent on direct contact between fungi and epithelial cells. Likewise, we 
      observed that TLR2 is important to downmodulate alpha3 integrin levels after 24 h of 
      infection. Thus, P. brasiliensis can modulate the host inflammatory response by 
      exploiting host cell receptors and cell signalling pathways.
FAU - de Barros, Bianca Carla Silva Campitelli
AU  - de Barros BCSC
AD  - Department of Microbiology, Immunology, and Parasitology, Escola Paulista de 
      Medicina, Universidade Federal de Sao Paulo, Sao Paulo, 04023-062, Brazil.
FAU - Almeida, Bruna Rocha
AU  - Almeida BR
AD  - Department of Microbiology, Immunology, and Parasitology, Escola Paulista de 
      Medicina, Universidade Federal de Sao Paulo, Sao Paulo, 04023-062, Brazil.
FAU - Suzuki, Erika
AU  - Suzuki E
AD  - Department of Microbiology, Immunology, and Parasitology, Escola Paulista de 
      Medicina, Universidade Federal de Sao Paulo, Sao Paulo, 04023-062, Brazil. 
      erika.suzuki@unifesp.br.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20201110
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Integrin alpha3)
RN  - 0 (TLR2 protein, human)
RN  - 0 (Toll-Like Receptor 2)
SB  - IM
MH  - A549 Cells
MH  - Blotting, Western
MH  - Epithelial Cells/*metabolism/microbiology
MH  - Host-Pathogen Interactions
MH  - Humans
MH  - Integrin alpha3/*metabolism
MH  - Lung/*metabolism/microbiology/pathology
MH  - Paracoccidioides/physiology
MH  - Toll-Like Receptor 2/*metabolism
PMC - PMC7655819
COIS- The authors declare no competing interests.
EDAT- 2020/11/12 06:00
MHDA- 2021/03/23 06:00
PMCR- 2020/11/10
CRDT- 2020/11/11 05:53
PHST- 2019/12/10 00:00 [received]
PHST- 2020/10/29 00:00 [accepted]
PHST- 2020/11/11 05:53 [entrez]
PHST- 2020/11/12 06:00 [pubmed]
PHST- 2021/03/23 06:00 [medline]
PHST- 2020/11/10 00:00 [pmc-release]
AID - 10.1038/s41598-020-76557-6 [pii]
AID - 76557 [pii]
AID - 10.1038/s41598-020-76557-6 [doi]
PST - epublish
SO  - Sci Rep. 2020 Nov 10;10(1):19483. doi: 10.1038/s41598-020-76557-6.