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

Autor:	Rana A; Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil.; Instituto de Investigação em Imunologia, Instituto Nacional de Ciência e Tecnologia (INCT), São Paulo, Brazil., de Almeida FC; Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil.; Instituto de Investigação em Imunologia, Instituto Nacional de Ciência e Tecnologia (INCT), São Paulo, Brazil., Paico Montero HA; Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil., Gonzales Carazas MM; Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil., Bortoluci KR; Departamento de Ciências Biológicas, Centro de Terapia Celular e Molecular (CTC-Mol), Universidade Federal de São Paulo, São Paulo, Brazil., Sad S; Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada., Amarante-Mendes GP; Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil.; Instituto de Investigação em Imunologia, Instituto Nacional de Ciência e Tecnologia (INCT), São Paulo, Brazil.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2020 Apr 09; Vol. 11, pp. 536. Date of Electronic Publication: 2020 Apr 09 (Print Publication: 2020).
DOI:	10.3389/fimmu.2020.00536
Abstrakt:	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. (Copyright © 2020 Rana, Campos de Almeida, Paico Montero, Gonzales Carazas, Bortoluci, Sad and Amarante-Mendes.)
Databáze:	MEDLINE
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