Experimental Therapy of Paracoccidioidomycosis Using P10-Primed Monocyte-Derived Dendritic Cells Isolated From Infected Mice

Autor(es)

Silva, Leandro B. R. ^[1] ; Taira, Cleison L. ^[2] ; Dias, Lucas S. ^{[2, 3]} ; Souza, Ana C. O. ^{[2, 4]} ; Nosanchuk, Joshua D. ^{[5, 6]} ; Travassos, Luiz R. ^[7] ; Taborda, Carlos P. ^{[2, 1]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Trop Med, Lab Med Mycol, USP LIM53, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Inst Biomed Sci, Dept Microbiol, Sao Paulo - Brazil

^[3] Univ Wisconsin, Sch Med & Publ Hlth, Dept Pediat, Madison, WI - USA

^[4] Univ Tennessee, Hlth Sci Ctr, Dept Clin Pharm & Translat Sci, Memphis, TN 38163 - USA

^[5] Albert Einstein Coll Med, Dept Med, Div Infect Dis, New York, NY - USA

^[6] Albert Einstein Coll Med, Microbiol & Immunol, New York, NY - USA

^[7] Univ Fed Sao Paulo, Dept Microbiol Immunol & Parasitol, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: FRONTIERS IN MICROBIOLOGY; v. 10, JUL 31 2019.
• Citações Web of Science: 0

Resumo

Paracoccidioidomycosis (PCM) is an endemic mycosis in Latin American caused by the thermodimorphic fungi of the genus Paracoccidioides spp. Notably, a Th1 immune response is required to control PCM. In this context, dendritic cells (DCs) seem to be essential players in capture, processing and presentation of Paracoccidioides antigens to naive T cells and their further activation. We have previously demonstrated that differentiated DCs from bone marrow cells, pulsed with the immunoprotective peptide 10 (P10), effectively control experimental PCM immunocompetent and immunosuppressed mice. However, this procedure may not be infeasible or it is limited for the therapy of human patients. Therefore, we have sought a less invasive but equally effective approach that would better mimics the autologous transplant of DC in a human patient. Here, we isolated and generated monocyte differentiated dendritic cells (MoDCs) from infected mice, pulsed them with P-10, and used them in the therapy of PCM in syngeneic mice. Similar to the results using BMDCs, the P10-pulsed MoDCs stimulated the proliferation of CD4(+) T lymphocytes, induced a mixed production of Th-1/Th-2 cytokines and decreased the fungal burden in murine lungs in the setting of PCM. The process of differentiating MoDCs derived from an infected host, and subsequently used for therapy of PCM is much simpler than that for obtaining BMDCs, and represents a more reasonable approach to treat patients infected with Paracoccidioides. The results presented suggest that P10-primed MoDC may be a promising strategy to combat complicated PCM as well as to significantly shorten the lengthy requirements for treatment of patients with this fungal disease. (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