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Identification of Potentially Therapeutic Immunogenic Peptides From Paracoccidioides lutzii Species
Leandro B R Silva1,2, Cleison L Taira1, Levi G Cleare2
1Departamento de Microbiologia, Instituto de Ciencias Biomedicas, Universidade de Sao Paulo, Sao Paulo, Brazil.
Abstract:
Paracoccidioidomycosis (PCM) is an endemic mycosis in Latin America caused by the thermodimorphic fungi of the genus Paracoccidioides spp. Paracoccidioides lutzii (PL) is one of the 5 species that constitute the Paracoccidioides genus. PL expresses low amounts of glycoprotein (Gp) 43 (PLGp43) and PLGp43 displays few epitopes in common with the P. brasiliensis (PB) immunodominant antigen PBGp43, which is commonly used for serological diagnosis of PCM. This difference in structure between the glycoproteins markedly reduces the efficiency of serological diagnosis in patients infected with PL. We previously demonstrated that peptide 10 (P10) from the PBGp43 induces protective immune responses in in vitro and in vivo models of PB PCM. Since, P10 has proven to be a promising therapeutic to combat PB, we sought to identify peptides in PL that could similarly be applied for the treatment of PCM. PL yeast cell proteins were isolated from PL: dendritic cell co-cultures and subjected to immunoproteomics. This approach identified 18 PL peptides that demonstrated in silico predictions for immunogenicity. Eight of the most promising peptides were synthesized and applied to lymphocytes obtained from peptide-immunized or PL-infected mice as well as to in vitro cultures with peptides or dendritic cells pulsed the peptides. The peptides LBR5, LBR6 and LBR8 efficiently promoted CD4+ and CD8+ T cell proliferation and dendritic cells pulsed with LBR1, LBR3, LBR7 or LBR8 stimulated CD4+ T cell proliferation. We observed increases of IFN-γ in the supernatants from primed T cells for the conditions with peptides without or with dendritic cells, although IL-2 levels only increased in response to LBR8. These novel immunogenic peptides derived from PL will be employed to develop new peptide vaccine approaches and the proteins from which they are derived can be used to develop new diagnostic assays for PL and possibly other Paracoccidioides spp. These findings identify and characterize new peptides with a promising therapeutic profile for future against this important neglected systemic mycosis.
Insights
New peptides from Paracoccidioides lutzii (PL) show promise for treating Paracoccidioidomycosis (PCM). These immunogenic peptides can be used to develop novel peptide vaccines and diagnostic tools for this neglected fungal infection.
Area of Science:
- Mycology
- Immunology
- Infectious Diseases
Background:
- Paracoccidioidomycosis (PCM) is a Latin American endemic mycosis caused by *Paracoccidioides* spp.
- Diagnosis is challenging for infections caused by *Paracoccidioides lutzii* (PL) due to low glycoprotein 43 (Gp43) expression and limited epitope homology with *P. brasiliensis* (PB) Gp43.
- Previous research identified a protective peptide (P10) from PB Gp43 for PB PCM treatment.
Purpose of the Study:
- To identify and characterize immunogenic peptides from *Paracoccidioides lutzii* (PL) for potential therapeutic applications in PCM.
- To evaluate the ability of these novel peptides to stimulate T cell responses.
Main Methods:
- Proteins from PL yeast cells were isolated and subjected to immunoproteomics to identify immunogenic peptides.
- Eight promising peptides were synthesized and tested for their ability to induce T cell proliferation (CD4+ and CD8+) and cytokine production (IFN-γ, IL-2) in mouse lymphocytes and dendritic cell co-cultures.
- In silico predictions were used to assess peptide immunogenicity.
Main Results:
- Immunoproteomics identified 18 potentially immunogenic PL peptides.
- Peptides LBR5, LBR6, and LBR8 induced significant CD4+ and CD8+ T cell proliferation.
- Dendritic cells pulsed with peptides LBR1, LBR3, LBR7, and LBR8 stimulated CD4+ T cell proliferation, with increased IFN-γ production observed.
- IL-2 production was specifically enhanced by LBR8.
Conclusions:
- Novel immunogenic peptides derived from *Paracoccidioides lutzii* have been identified.
- These peptides demonstrate therapeutic potential for developing new peptide vaccines against PCM.
- The identified peptides and their source proteins may also aid in developing improved diagnostic assays for PL and other *Paracoccidioides* species.
