Intestinal host defense outcome is dictated by PGE(2) production during efferocytosis of infected cells

Autor(es):Mostrar menos -

Dejani, Naiara Naiana ^{[1, 2]} ; Orlando, Allan Botinhon ^[2] ; Nino, Victoria Eugenia ^[2] ; Penteado, Leticia de Aquino ^[2] ; Verdan, Felipe Fortino ^{[1, 2]} ; Ribeiro Bazzano, Julia Miranda ^[2] ; Codo, Ana Campos ^[2] ; Guerta Salina, Ana Carolina ^{[1, 2]} ; Saraiva, Amanda Correia ^[2] ; Avelar, Matheus Rossi ^[2] ; Spolidorio, Luis Carlos ^[3] ; Serezani, C. Henrique ^[4] ; Medeiros, Alexandra Ivo ^[2]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Biochem & Immunol, BR-14049900 Ribeirao Preto, SP - Brazil

^[2] Sao Paulo State Univ, Sch Pharmaceut Sci, Dept Biol Sci, BR-01049010 Araraquara, SP - Brazil

^[3] Sao Paulo State Univ, Sch Dent, Dept Physiol & Pathol, BR-01049010 Araraquara, SP - Brazil

^[4] Vanderbilt Univ, Med Ctr, Div Infect Dis, Dept Med, Nashville, TN 37232 - USA

• Tipo de documento: Artigo Científico
• Fonte: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA; v. 115, n. 36, p. E8469-E8478, SEP 4 2018.
• Citações Web of Science: 3

Resumo

Inflammatory responses are terminated by the clearance of dead cells, a process termed efferocytosis. A consequence of efferocytosis is the synthesis of the antiinflammatory mediators TGF-beta, PGE(2), and IL-10; however, the efferocytosis of infected cells favors Th17 responses by eliciting the synthesis of TGF-beta, IL-6, and IL-23. Recently, we showed that the efferocytosis of apoptotic Escherichia coli-infected macrophages by dendritic cells triggers PGE(2) production in addition to pro-Th17 cytokine expression. We therefore examined the role of PGE(2) during Th17 differentiation and intestinal pathology. The efferocytosis of apoptotic E. coli-infected cells by dendritic cells promoted high levels of PGE(2), which impaired IL-1R expression via the EP4-PKA pathway in T cells and consequently inhibited Th17 differentiation. The outcome of murine intestinal Citrobacter rodentium infection was dependent on the EP4 receptor. Infected mice treated with EP4 antagonist showed enhanced intestinal defense against C. rodentium compared with infected mice treated with vehicle control. Those results suggest that EP4 signaling during infectious colitis could be targeted as a way to enhance Th17 immunity and host defense. (AU)

• Processo FAPESP: 16/10964-5 - Mecanismo pelo qual PGE2 oriunda da eferocitose inibe a expressão do IL-1R e a diferenciação de Th17 - Envolvimento de SOCS3
• Beneficiário: Allan Botinhon Orlando
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 11/17611-7 - Efeito da fagocitose de células apoptóticas por células dendríticas na diferenciação de células Th17: função de PGE2
• Beneficiário: Alexandra Ivo de Medeiros
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 12/23580-0 - Diferenciação de células Th17 durante a fagocitose de células apoptóticas infectadas: determinação das vias de sinalização intracelular via PGE2 e receptores EP
• Beneficiário: Naiara Naiana Dejani
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 14/03967-2 - Perfil fenotípico e capacidade migratória de células dendríticas após fagocitose de células apoptóticas
• Beneficiário: Letícia de Aquino Penteado
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica