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Article

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

1
Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-000, Brazil
2
Departments of Medicine (Division of Infectious Diseases), Microbiology and Immunology, Albert Einstein College of Medicine, New York, NY 10461, USA
3
Laboratory of Medical Mycology, Tropical Medicine Institute USP-LIM53, University of São Paulo, São Paulo 05403-000, Brazil
*
Author to whom correspondence should be addressed.
Academic Editor: Joseph M. Bliss
J. Fungi 2021, 7(6), 416; https://doi.org/10.3390/jof7060416
Received: 4 May 2021 / Revised: 21 May 2021 / Accepted: 23 May 2021 / Published: 26 May 2021
(This article belongs to the Special Issue Host Defense against Fungi)
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-γ and TNF-α, 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. View Full-Text
Keywords: neutrophils 1; P10 2; vaccine 3; DODAB 4; paracoccidioides brasiliensis 5; paracoccidioidomycosis 6; neutrophil depletion 7 neutrophils 1; P10 2; vaccine 3; DODAB 4; paracoccidioides brasiliensis 5; paracoccidioidomycosis 6; neutrophil depletion 7
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MDPI and ACS Style

Dias, L.d.S.; Silva, L.B.R.; Nosanchuk, J.D.; Taborda, C.P. Neutrophil Cells Are Essential for The Efficacy of a Therapeutic Vaccine against Paracoccidioidomycosis. J. Fungi 2021, 7, 416. https://doi.org/10.3390/jof7060416

AMA Style

Dias LdS, Silva LBR, Nosanchuk JD, Taborda CP. Neutrophil Cells Are Essential for The Efficacy of a Therapeutic Vaccine against Paracoccidioidomycosis. Journal of Fungi. 2021; 7(6):416. https://doi.org/10.3390/jof7060416

Chicago/Turabian Style

Dias, Lucas d.S., Leandro B.R. Silva, Joshua D. Nosanchuk, and Carlos P. Taborda 2021. "Neutrophil Cells Are Essential for The Efficacy of a Therapeutic Vaccine against Paracoccidioidomycosis" Journal of Fungi 7, no. 6: 416. https://doi.org/10.3390/jof7060416

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