RIP2 Contributes to Expanded CD4+ T Cell IFN-g Production during Efferocytosis of Streptococcus pneumoniae–Infected Apoptotic Cells

• Autor(a) principal: Niño-Castaño, Victoria Eugenia [UNESP]
• Data de Publicação: 2022
• Outros Autores: de Aquino Penteado, Letícia [UNESP], Silva-Pereira, Ludmilla [UNESP], Bazzano, Júlia Miranda Ribeiro [UNESP], Orlando, Allan Botinhon [UNESP], Salina, Ana Carolina Guerta [UNESP], Dejani, Naiara Naiana, Bonato, Vânia L.D., Serezani, C. Henrique, Medeiros, Alexandra Ivo [UNESP]
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UNESP
• Texto Completo: http://dx.doi.org/10.4049/immunohorizons.2200001; http://hdl.handle.net/11449/241434

Apoptotic cell clearance by professional and nonprofessional phagocytes in the process of efferocytosis is critical to preserve tissue homeostasis. Uptake of apoptotic cells by dendritic cells generates regulatory T cells and induces immunologic tolerance against self-antigens. In contrast, ingestion of infected apoptotic cells promotes activation of TLR4/MyD88-dependent bone marrow–derived dendritic cells (BMDCs) and triggers Th17 cell differentiation. In this study, we evaluated the impact of Streptococcus pneumoniae–infected apoptotic cell efferocytosis by BMDCs derived from C57BL/6 mice on differentiation and expansion of CD4+ T cell subsets, as well as the role of TLR2/4 and receptor-interacting protein 2 (RIP2) receptors in recognizing intracellular pathogens during efferocytosis. We demonstrated that BMDC-mediated efferocytosis of S. pneumoniae–infected apoptotic cells induced Th1 cell differentiation and expansion. Although TLR2/4 and RIP2 deficiency in BMDCs did not affect Th1 cell differentiation during efferocytosis, the absence of RIP2 decreased IFN-γ production by CD4 T cells during the expansion phase. These findings suggest that RIP2-mediated IL-1β production during efferocytosis of S. pneumoniae–infected apoptotic cells partially supports a Th1-mediated IFN-γ production microenvironment.