PMID- 34073466
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210627
IS  - 2309-608X (Electronic)
IS  - 2309-608X (Linking)
VI  - 7
IP  - 6
DP  - 2021 May 26
TI  - Neutrophil Cells Are Essential for The Efficacy of a Therapeutic Vaccine against 
      Paracoccidioidomycosis.
LID - 10.3390/jof7060416 [doi]
LID - 416
AB  - Paracoccidioidomycosis (PCM), caused by the Paracoccidioides species, is a 
      systemic disease endemic in several Latin American countries, mainly in Brazil, 
      Colombia, Argentina, and Venezuela. Current treatment approaches are challenging 
      as they require prolonged durations of antifungal drugs that have potential 
      toxicities, and despite antifungals, relapses are common. Hence, new therapeutic 
      approaches, such as vaccines, are being investigated. The therapeutic vaccine 
      consisting of peptide P10 associated with lipid cationic DODAB (P10+DODAB) is 
      effective in murine models of PCM. However, the specific immune mechanisms 
      required for the protective response has not been fully elucidated. The present 
      work aims at evaluating the participation of neutrophils in the immune response 
      induced by P10+DODAB. We found that the vaccine reduced both the influx of 
      pulmonary neutrophils and the fungal load in comparison to infected animals that 
      did not receive this treatment. The parenchymal architecture of the lungs of 
      P10+DODAB-treated animals was largely preserved with only a few granulomas 
      present, and tissue cytokine analysis showed a Th1 cytokine profile with 
      augmented levels of IL-12, IFN-gamma and TNF-alpha, and low levels of IL-4. When 
      neutrophils were depleted 24 h prior to each treatment, the effectiveness of the 
      P10+DODAB vaccine was completely lost as the fungal burdens remained high and 
      histological examination showed a marked inflammation and fungal dissemination 
      with a dysregulated cytokine response. In conclusion, these findings indicate 
      that neutrophils are vital to ensure the triggering of an effective immune 
      response to P10+DODAB.
FAU - Dias, Lucas Dos Santos
AU  - Dias LDS
AUID- ORCID: 0000-0003-2344-1354
AD  - Department of Microbiology, Institute of Biomedical Sciences, University of Sao 
      Paulo, Sao Paulo 05508-000, Brazil.
FAU - Silva, Leandro B R
AU  - Silva LBR
AD  - Department of Microbiology, Institute of Biomedical Sciences, University of Sao 
      Paulo, Sao Paulo 05508-000, Brazil.
FAU - Nosanchuk, Joshua D
AU  - Nosanchuk JD
AUID- ORCID: 0000-0001-9905-5754
AD  - Departments of Medicine (Division of Infectious Diseases), Microbiology and 
      Immunology, Albert Einstein College of Medicine, New York, NY 10461, USA.
FAU - Taborda, Carlos Pelleschi
AU  - Taborda CP
AUID- ORCID: 0000-0001-9928-9809
AD  - Department of Microbiology, Institute of Biomedical Sciences, University of Sao 
      Paulo, Sao Paulo 05508-000, Brazil.
AD  - Laboratory of Medical Mycology, Tropical Medicine Institute USP-LIM53, University 
      of Sao Paulo, Sao Paulo 05403-000, Brazil.
LA  - eng
GR  - 2016/08730-6/Fundacao de Amparo a Pesquisa do Estado de Sao Paulo/
GR  - 2018/25171-6/Fundacao de Amparo a Pesquisa do Estado de Sao Paulo/
GR  - 420480/2018-8/Conselho Nacional de Desenvolvimento Cientifico e Tecnologico/
PT  - Journal Article
DEP - 20210526
PL  - Switzerland
TA  - J Fungi (Basel)
JT  - Journal of fungi (Basel, Switzerland)
JID - 101671827
PMC - PMC8226764
OTO - NOTNLM
OT  - DODAB 4
OT  - P10 2
OT  - neutrophil depletion 7
OT  - neutrophils 1
OT  - paracoccidioides brasiliensis 5
OT  - paracoccidioidomycosis 6
OT  - vaccine 3
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflicts of interest.
EDAT- 2021/06/03 06:00
MHDA- 2021/06/03 06:01
PMCR- 2021/05/26
CRDT- 2021/06/02 01:38
PHST- 2021/05/04 00:00 [received]
PHST- 2021/05/21 00:00 [revised]
PHST- 2021/05/23 00:00 [accepted]
PHST- 2021/06/02 01:38 [entrez]
PHST- 2021/06/03 06:00 [pubmed]
PHST- 2021/06/03 06:01 [medline]
PHST- 2021/05/26 00:00 [pmc-release]
AID - jof7060416 [pii]
AID - jof-07-00416 [pii]
AID - 10.3390/jof7060416 [doi]
PST - epublish
SO  - J Fungi (Basel). 2021 May 26;7(6):416. doi: 10.3390/jof7060416.