RIPK3 and Caspase-1/11 Are Necessary for Optimal Antigen-Specific CD8 T Cell Response Elicited by Genetically Modified Listeria monocytogenes

Autor(es)

Rana, Aamir ^{[1, 2]} ; de Almeida, Felipe Campos ^{[1, 2]} ; Paico Montero, Henry A. ^[2] ; Gonzales Carazas, Maryanne M. ^[2] ; Bortoluci, Karina R. ^[3] ; Sad, Subash ^[4] ; Amarante-Mendes, Gustavo P. ^{[1, 2]}

Afiliação do(s) autor(es)

^[1] INCT, Inst Invest Imunol, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Inst Ciencias Biomed, Sao Paulo - Brazil

^[3] Univ Fed Sao Paulo, Dept Ciencias Biol, Ctr Terapia Celular & Mol CTC Mol, Sao Paulo - Brazil

^[4] Univ Ottawa, Dept Biochem Microbiol & Immunol, Fac Med, Ottawa, ON - Canada

• Tipo de documento: Artigo Científico
• Fonte: FRONTIERS IN IMMUNOLOGY; v. 11, APR 9 2020.
• Citações Web of Science: 0

Resumo

Efficient induction of effector and long-term protective antigen-specific CD8(+) T memory response by vaccination is essential to eliminate malignant and pathogen-infected cells. Intracellular infectious bacteria, including Listeria monocytogenes, have been considered potent vectors to carry multiple therapeutic proteins and generate antigen-specific CD8(+) T cell responses. Although the role of molecules involved in inflammatory cell death pathways, such as necroptosis (RIPK3-mediated) and pyroptosis (Caspase-1/11-mediated), as effectors of immune response against intracellular bacteria are relatively well understood, their contribution to the adjuvant effect of recombinant bacterial vectors in the context of antigen-specific CD8(+) T cell response remained obscure. Therefore, we evaluated the impact of RIPK3 and Caspase-1/11 (Casp-1/11) individual and combined deficiencies on the modulation of antigen-specific CD8(+) T cell response during vaccination of mice with ovalbumin-expressing L. monocytogenes (LM-OVA). We observed that Casp-1/11 but not RIPK3 deficiency negatively impacts the capacity of mice to clear LM-OVA. Importantly, both RIPK3 and Casp-1/11 are necessary for optimal LM-OVA-mediated antigen-specific CD8(+) T cell response, as measured by in vivo antigen-specific CD8(+) T cell proliferation, target cell elimination, and cytokine production. Furthermore, Casp-1/11 and Casp-1/11/RIPK3 combined deficiencies restrict the early initiation of antigen-specific CD8(+) T cell memory response. Taken together, our findings demonstrate that RIPK3 and Casp-1/11 influence the quality of CD8(+) T cell responses induced by recombinant L. monocytogenes vectors. (AU)

• Processo FAPESP: 15/12977-4 - Modulação da resposta anti-tumoral por agentes infecciosos modificados geneticamente
• Beneficiário: Aamir Rana
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 18/01627-0 - Modulação anti-tumoral, resposta imune mediada pelas células T CD8 por agentes infecciosos geneticamente modificados
• Beneficiário: Aamir Rana
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado