Neutrophil Cells Are Essential for The Efficacy of a Therapeutic Vaccine against Paracoccidioidomycosis

Autor(es)

Dias, Lucas dos Santos ^[1] ; Silva, Leandro B. R. ^[1] ; Nosanchuk, Joshua D. ^[2] ; Taborda, Carlos Pelleschi ^{[1, 3]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Microbiol, BR-05508000 Sao Paulo - Brazil

^[2] Albert Einstein Coll Med, Dept Med, Div Infect Dis Microbiol & Immunol, New York, NY 10461 - USA

^[3] Univ Sao Paulo, Trop Med Inst USP LIM53, Lab Med Mycol, BR-05403000 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF FUNGI; v. 7, n. 6 JUN 2021.
• Citações Web of Science: 0

Resumo

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. (AU)

• Processo FAPESP: 18/25171-6 - Prospecção de novos epitopos com potencial vacinal no controle da infecção experimental por Paracoccidioides lutzii
• Beneficiário: Leandro Buffoni Roque da Silva
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 16/08730-6 - Patogenicidade fúngica: efeito do tabagismo, resposta imune e a modulação vacinal na paracoccidioidomicose e na histoplasmose
• Beneficiário: Carlos Pelleschi Taborda
• Modalidade de apoio: Auxílio à Pesquisa - Temático