PMID- 37524886
OWN - NLM
STAT- MEDLINE
DCOM- 20230803
LR  - 20230803
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 13
IP  - 1
DP  - 2023 Jul 31
TI  - The immunosuppressive activity of myeloid-derived suppressor cells in murine 
      Paracoccidioidomycosis relies on Indoleamine 2,3-dioxygenase activity and 
      Dectin-1 and TLRs signaling.
PG  - 12391
LID - 10.1038/s41598-023-39262-8 [doi]
LID - 12391
AB  - Paracoccidioidomycosis (PCM) is a systemic mycosis with a high incidence in Latin 
      America. Prior studies have demonstrated the significance of the enzyme 
      Indoleamine 2,3-dioxygenase (IDO-1) in the immune regulation of PCM as well as 
      the vital role of myeloid-derived suppressor cells (MDSCs) in moderating PCM 
      severity. Additionally, Dectin-1 and Toll-Like Receptors (TLRs) signaling in 
      cancer, infection, and autoimmune diseases have been shown to impact 
      MDSC-IDO-1(+) activity. To expand our understanding of MDSCs and the role of 
      IDO-1 and pattern recognition receptors (PRRs) signaling in PCM, we generated 
      MDSCs in vitro and administered an IDO-1 inhibitor before challenging the cells 
      with Paracoccidioides brasiliensis yeasts. By co-culturing MDSCs with 
      lymphocytes, we assessed T-cell proliferation to examine the influence of IDO-1 
      on MDSC activity. Moreover, we utilized specific antibodies and MDSCs from 
      Dectin-1, TLR4, and TLR2 knockout mice to evaluate the effect of these PRRs on 
      IDO-1 production by MDSCs. We confirmed the importance of these in vitro findings 
      by assessing MDSC-IDO-1(+) in the lungs of mice following the fungal infection. 
      Taken together, our data show that IDO-1 expression by MDSCs is crucial for the 
      control of T-cell proliferation, and the production of this enzyme is partially 
      dependent on Dectin-1, TLR2, and TLR4 signaling during murine PCM.
CI  - (c) 2023. The Author(s).
FAU - Kaminski, Valeria de Lima
AU  - Kaminski VL
AD  - Institute of Science and Technology, Federal University of Sao Paulo - UNIFESP, 
      Sao Jose dos Campos, SP, Brazil.
FAU - Preite, Nycolas Willian
AU  - Preite NW
AD  - Institute of Science and Technology, Federal University of Sao Paulo - UNIFESP, 
      Sao Jose dos Campos, SP, Brazil.
FAU - Borges, Bruno Montanari
AU  - Borges BM
AD  - Institute of Science and Technology, Federal University of Sao Paulo - UNIFESP, 
      Sao Jose dos Campos, SP, Brazil.
FAU - Dos Santos, Bianca Vieira
AU  - Dos Santos BV
AD  - Institute of Science and Technology, Federal University of Sao Paulo - UNIFESP, 
      Sao Jose dos Campos, SP, Brazil.
FAU - Calich, Vera Lucia Garcia
AU  - Calich VLG
AD  - Department of Immunology, Institute of Biomedical Sciences, University of Sao 
      Paulo - USP, Sao Paulo, Brazil.
FAU - Loures, Flavio Vieira
AU  - Loures FV
AD  - Institute of Science and Technology, Federal University of Sao Paulo - UNIFESP, 
      Sao Jose dos Campos, SP, Brazil. loures@unifesp.br.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230731
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (dectin 1)
RN  - 0 (Indoleamine-Pyrrole 2,3,-Dioxygenase)
RN  - 0 (Toll-Like Receptor 2)
RN  - 0 (Toll-Like Receptor 4)
SB  - IM
MH  - Animals
MH  - Mice
MH  - *Myeloid-Derived Suppressor Cells
MH  - *Paracoccidioidomycosis
MH  - Indoleamine-Pyrrole 2,3,-Dioxygenase/metabolism
MH  - Toll-Like Receptor 2/metabolism
MH  - Toll-Like Receptor 4/metabolism
MH  - Mice, Knockout
PMC - PMC10390561
COIS- The authors declare no competing interests.
EDAT- 2023/08/01 01:08
MHDA- 2023/08/03 06:43
PMCR- 2023/07/31
CRDT- 2023/07/31 23:26
PHST- 2023/04/28 00:00 [received]
PHST- 2023/07/22 00:00 [accepted]
PHST- 2023/08/03 06:43 [medline]
PHST- 2023/08/01 01:08 [pubmed]
PHST- 2023/07/31 23:26 [entrez]
PHST- 2023/07/31 00:00 [pmc-release]
AID - 10.1038/s41598-023-39262-8 [pii]
AID - 39262 [pii]
AID - 10.1038/s41598-023-39262-8 [doi]
PST - epublish
SO  - Sci Rep. 2023 Jul 31;13(1):12391. doi: 10.1038/s41598-023-39262-8.