Titan Cells and Yeast Forms of Cryptococcus neoformans and Cryptococcus gattii Are Recognized by GXMR-CAR

Autor(es)

dos Santos, Matheus Henrique ^[1] ; Machado, Michele Procopio ^[1] ; Kumaresan, Pappanaicken R. ^[2] ; da Silva, Thiago Aparecido ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Cell & Mol Biol & Pathogen Bioagents, BR-14049090 Ribeirao Preto, SP - Brazil

^[2] Univ Texas MD Anderson Canc Ctr, Dept Lymphoma & Myeloma, Houston, TX 77030 - USA

• Tipo de documento: Artigo Científico
• Fonte: MICROORGANISMS; v. 9, n. 9 SEP 2021.
• Citações Web of Science: 0

Resumo

Cryptococcosis, a systemic mycosis that affects both the immunocompromised and immunocompetent, is caused by the inhalation of dehydrated yeasts or fungal spores of Cryptococcus gattii or Cryptococcus neoformans. The Cryptococcus spp. polysaccharide capsule is composed mainly of glucuronoxylomannan-GXM, its major virulence factor. The capsule thickness increases to more than 15 mu m during titanization, favoring the pathogenesis of cryptococcosis. Previous studies demonstrated that cytotoxic T cells that had been bioengineered with GXM-targeting chimeric antigen receptor (GXMR-CAR) were able to recognize C. neoformans by promoting the control of titanization. GXMR-CAR, a second-generation CAR, contains a single-chain variable fragment that originates from a 18B7 clone: a human IgG4 hinge, followed by a human CD28 (transmembrane/cytoplasmic domains) and a CD3 sigma chain. In the current study, we redirected T cells to target distinct C. neoformans and C. gattii cell types by GXMR-CAR. Lentiviral particles carrying the GXMR-CAR sequence were used to transduce Jurkat cells, and these modified cells interacted with the GXM of the C. gattii R265 strain. Moreover, GXMR-CAR mediated the recognition of C. gattii and C. neoformans yeasts with both thin and thick polysaccharide capsules, and GXMR-CAR Jurkat cells interacted with titan cells sourced from both Cryptococcus spp. Thus, bioengineered cells using CAR can improve the treatment of cryptococcosis. (AU)

• Processo FAPESP: 18/18538-0 - Bioengenharia de células T e NK através de receptores CAR contra infecções fúngicas invasivas
• Beneficiário: Thiago Aparecido da Silva
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 20/09113-6 - Atividade funcional de células T modificadas com GXMR-CAR expressando a porção intracelular de CD28 ou CD137, no controle da criptococose experimental
• Beneficiário: Matheus Henrique dos Santos
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 19/26074-7 - Bioengenharia de células T e NK através de receptores CAR contra infecções fúngicas invasivas
• Beneficiário: Thiago Aparecido da Silva
• Modalidade de apoio: Bolsas no Brasil - Jovens Pesquisadores
• Processo FAPESP: 20/11307-3 - Impacto de distintos scFv em GXMR-CAR expresso por linfócitos T na etapa de ativação celular frente a Cryptococcus spp
• Beneficiário: Michele Procópio Machado
• Modalidade de apoio: Bolsas no Brasil - Mestrado