PMID- 28871251
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20191120
IS  - 1664-3224 (Print)
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 8
DP  - 2017
TI  - Th17-Inducing Cytokines IL-6 and IL-23 Are Crucial for Granuloma Formation during 
      Experimental Paracoccidioidomycosis.
PG  - 949
LID - 10.3389/fimmu.2017.00949 [doi]
LID - 949
AB  - Paracoccidioidomycosis (PCM), a chronic granulomatous disease caused by the 
      thermally dimorphic fungus Paracoccidioides brasiliensis and Paracoccidioides 
      lutzii, has the highest mortality rate among systemic mycosis. The T helper 
      1-mediated immunity is primarily responsible for acquired resistance during P. 
      brasiliensis infection, while susceptibility is associated with Th2 occurrence. 
      Th17 is a population of T CD4(+) cells that, among several chemokines and 
      cytokines, produces IL-17A and requires the presence of IL-1, IL-6, and TGF-beta for 
      differentiation in mice and IL-23 for its maintenance. Th17 has been described as 
      an arm of the immune system that enhances host protection against several 
      bacterial and fungal infections, as Pneumocystis carinii and Candida albicans. In 
      this study, we aimed to evaluate the Th17 immune response and the role of 
      Th17-associated cytokines (IL-6, IL-23, and IL-17A) during experimental PCM. 
      First, we observed that P. brasiliensis infection [virulent yeast strain 18 of P. 
      brasiliensis (Pb18)] increased the IL-17A production in vitro and all the 
      evaluated Th17-associated cytokines in the lung tissue from C57BL/6 wild-type 
      mice. In addition, the deficiency of IL-6, IL-23, or IL-17 receptor A (IL-17RA) 
      impaired the compact granuloma formation and conferred susceptibility during 
      infection, associated with reduced tumor necrosis factor-alpha, IFN-gamma, and inducible 
      nitric oxide synthase enzyme expression. Our data suggest that IL-6 production by 
      bone marrow-derived macrophages (BMDMs) is important to promote the Th17 
      differentiation during Pb18 infection. In accordance, the adoptive transfer of 
      BMDMs from C57BL/6 to infected IL-6(-/-) or IL-17RA(-/-) mice reduced the fungal 
      burden in the lungs compared to nontransferred mice and reestablished the 
      pulmonary granuloma formation. Taken together, these results suggest that 
      Th17-associated cytokines are involved in the modulation of immune response and 
      granuloma formation during experimental PCM.
FAU - Tristao, Fabrine Sales Massafera
AU  - Tristao FSM
AD  - Department of Biochemistry and Immunology, School of Medicine of Ribeirao Preto, 
      University of Sao Paulo, Ribeirao Preto, Brazil.
FAU - Rocha, Fernanda Agostini
AU  - Rocha FA
AD  - Department of Biochemistry and Immunology, School of Medicine of Ribeirao Preto, 
      University of Sao Paulo, Ribeirao Preto, Brazil.
FAU - Carlos, Daniela
AU  - Carlos D
AD  - Department of Biochemistry and Immunology, School of Medicine of Ribeirao Preto, 
      University of Sao Paulo, Ribeirao Preto, Brazil.
FAU - Ketelut-Carneiro, Natalia
AU  - Ketelut-Carneiro N
AD  - Department of Biochemistry and Immunology, School of Medicine of Ribeirao Preto, 
      University of Sao Paulo, Ribeirao Preto, Brazil.
FAU - Souza, Camila Oliveira Silva
AU  - Souza COS
AD  - Department of Biochemistry and Immunology, School of Medicine of Ribeirao Preto, 
      University of Sao Paulo, Ribeirao Preto, Brazil.
FAU - Milanezi, Cristiane Maria
AU  - Milanezi CM
AD  - Department of Biochemistry and Immunology, School of Medicine of Ribeirao Preto, 
      University of Sao Paulo, Ribeirao Preto, Brazil.
FAU - Silva, Joao Santana
AU  - Silva JS
AD  - Department of Biochemistry and Immunology, School of Medicine of Ribeirao Preto, 
      University of Sao Paulo, Ribeirao Preto, Brazil.
LA  - eng
PT  - Journal Article
DEP - 20170821
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
PMC - PMC5566564
OTO - NOTNLM
OT  - IL-17A
OT  - IL-23
OT  - IL-6
OT  - Th17
OT  - paracoccidioidomycosis
EDAT- 2017/09/06 06:00
MHDA- 2017/09/06 06:01
PMCR- 2017/01/01
CRDT- 2017/09/06 06:00
PHST- 2017/05/22 00:00 [received]
PHST- 2017/07/25 00:00 [accepted]
PHST- 2017/09/06 06:00 [entrez]
PHST- 2017/09/06 06:00 [pubmed]
PHST- 2017/09/06 06:01 [medline]
PHST- 2017/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2017.00949 [doi]
PST - epublish
SO  - Front Immunol. 2017 Aug 21;8:949. doi: 10.3389/fimmu.2017.00949. eCollection 
      2017.