PMID- 37233259
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230529
IS  - 2309-608X (Electronic)
IS  - 2309-608X (Linking)
VI  - 9
IP  - 5
DP  - 2023 May 10
TI  - Targeting the P10 Peptide in Maturing Dendritic Cells via the DEC205 Receptor In 
      Vivo: A New Therapeutic Strategy against Paracoccidioidomycosis.
LID - 10.3390/jof9050548 [doi]
LID - 548
AB  - Paracoccidioidomycosis (PCM) is a systemic mycosis caused by Paracoccidioides 
      brasiliensis, a thermally dimorphic fungus, which is the most frequent endemic 
      systemic mycosis in many Latin American countries, where ~10 million people are 
      believed to be infected. In Brazil, it is ranked as the tenth most common cause 
      of death among chronic infectious diseases. Hence, vaccines are in development to 
      combat this insidious pathogen. It is likely that effective vaccines will need to 
      elicit strong T cell-mediated immune responses composed of IFNgamma secreting CD4(+) 
      helper and CD8(+) cytolytic T lymphocytes. To induce such responses, it would be 
      valuable to harness the dendritic cell (DC) system of antigen-presenting cells. 
      To assess the potential of targeting P10, which is a peptide derived from gp43 
      secreted by the fungus, directly to DCs, we cloned the P10 sequence in fusion 
      with a monoclonal antibody to the DEC205 receptor, an endocytic receptor that is 
      abundant on DCs in lymphoid tissues. We verified that a single injection of the 
      alphaDEC/P10 antibody caused DCs to produce a large amount of IFNgamma. Administration of 
      the chimeric antibody to mice resulted in a significant increase in the levels of 
      IFN-gamma and IL-4 in lung tissue relative to control animals. In therapeutic assays, 
      mice pretreated with alphaDEC/P10 had significantly lower fungal burdens compared to 
      control infected mice, and the architecture of the pulmonary tissues of alphaDEC/P10 
      chimera-treated mice was largely normal. Altogether, the results obtained so far 
      indicate that targeting P10 through a alphaDEC/P10 chimeric antibody in the presence 
      of polyriboinosinic: polyribocytidylic acid is a promising strategy in 
      vaccination and therapeutic protocols to combat PCM.
FAU - Santos, Suelen S
AU  - Santos SS
AD  - Department of Clinical and Toxicological Analysis, Faculty of Pharmaceutical 
      Sciences, University of Sao Paulo, Sao Paulo 05508-000, SP, Brazil.
FAU - Rampazo, Eline
AU  - Rampazo E
AD  - Department of Parasitology, Biomedical Sciences Institute, University of Sao 
      Paulo, Sao Paulo 05508-000, SP, Brazil.
FAU - Taborda, Carlos P
AU  - Taborda CP
AUID- ORCID: 0000-0001-9928-9809
AD  - Department of Microbiology, Biomedical Sciences Institute, University of Sao 
      Paulo, Sao Paulo 05508-000, SP, Brazil.
FAU - Nosanchuk, Joshua D
AU  - Nosanchuk JD
AD  - Departments of Medicine, Division of Infectious Diseases, Microbiology and 
      Immunology, Albert Einstein College of Medicine and Montefiore Medical Center, 
      Bronx, NY 10461, USA.
FAU - Boscardin, Silvia B
AU  - Boscardin SB
AUID- ORCID: 0000-0002-7845-7110
AD  - Department of Parasitology, Biomedical Sciences Institute, University of Sao 
      Paulo, Sao Paulo 05508-000, SP, Brazil.
FAU - Almeida, Sandro R
AU  - Almeida SR
AUID- ORCID: 0000-0002-0562-1610
AD  - Department of Clinical and Toxicological Analysis, Faculty of Pharmaceutical 
      Sciences, University of Sao Paulo, Sao Paulo 05508-000, SP, Brazil.
LA  - eng
GR  - 2018/11624-9 / 12/16710-4 / 10/50439-0/Sao Paulo Research Foundation/
PT  - Journal Article
DEP - 20230510
PL  - Switzerland
TA  - J Fungi (Basel)
JT  - Journal of fungi (Basel, Switzerland)
JID - 101671827
PMC - PMC10219127
OTO - NOTNLM
OT  - DEC205
OT  - P10 peptide
OT  - Paracoccidioides brasiliensis
OT  - dendritic cells
OT  - paracoccidioidomycosis
COIS- The authors declare no conflict of interest.
EDAT- 2023/05/26 13:09
MHDA- 2023/05/26 13:10
PMCR- 2023/05/10
CRDT- 2023/05/26 10:03
PHST- 2023/03/14 00:00 [received]
PHST- 2023/04/27 00:00 [revised]
PHST- 2023/05/06 00:00 [accepted]
PHST- 2023/05/26 13:10 [medline]
PHST- 2023/05/26 13:09 [pubmed]
PHST- 2023/05/26 10:03 [entrez]
PHST- 2023/05/10 00:00 [pmc-release]
AID - jof9050548 [pii]
AID - jof-09-00548 [pii]
AID - 10.3390/jof9050548 [doi]
PST - epublish
SO  - J Fungi (Basel). 2023 May 10;9(5):548. doi: 10.3390/jof9050548.