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Role for Caspase-8 in the Release of IL-1ß and Active Caspase-1 from Viable Human Monocytes during Toxoplasma gondii Infection.
Pandori, William J; Matsuno, Stephanie Y; Shin, Ji-Hun; Kim, Samuel C; Kao, Tiffany H; Mallya, Sharmila; Batarseh, Sarah N; Lodoen, Melissa B.
Afiliación
  • Pandori WJ; Department of Molecular Biology & Biochemistry and the Institute for Immunology, University of California, Irvine, CA.
  • Matsuno SY; Department of Molecular Biology & Biochemistry and the Institute for Immunology, University of California, Irvine, CA.
  • Shin JH; Department of Molecular Biology & Biochemistry and the Institute for Immunology, University of California, Irvine, CA.
  • Kim SC; Department of Molecular Biology & Biochemistry and the Institute for Immunology, University of California, Irvine, CA.
  • Kao TH; Department of Molecular Biology & Biochemistry and the Institute for Immunology, University of California, Irvine, CA.
  • Mallya S; Department of Molecular Biology & Biochemistry and the Institute for Immunology, University of California, Irvine, CA.
  • Batarseh SN; Department of Molecular Biology & Biochemistry and the Institute for Immunology, University of California, Irvine, CA.
  • Lodoen MB; Department of Molecular Biology & Biochemistry and the Institute for Immunology, University of California, Irvine, CA.
J Immunol ; 212(7): 1161-1171, 2024 Apr 01.
Article en En | MEDLINE | ID: mdl-38372637
ABSTRACT
Monocytes are actively recruited to sites of infection and produce the potent proinflammatory cytokine IL-1ß. We previously showed that IL-1ß release during Toxoplasma gondii infection of primary human monocytes requires the NLRP3 inflammasome and caspase-1 but is independent of gasdermin D and pyroptosis. To investigate mechanisms of IL-1ß release, we generated caspase-1, -4, -5, or -8 knockout (KO) THP-1 monocytic cells. Genetic ablation of caspase-1 or -8, but not caspase-4 or -5, decreased IL-1ß release during T. gondii infection without affecting cell death. In contrast, TNF-α and IL-6 secretion were unperturbed in caspase-8 KO cells during T. gondii infection. Dual pharmacological inhibition of caspase-8 and RIPK1 in primary monocytes also decreased IL-1ß release without affecting cell viability or parasite infection. Caspase-8 was also required for the release of active caspase-1 from T. gondii-infected cells and for IL-1ß release during infection with the related apicomplexan parasite Neospora caninum. Surprisingly, caspase-8 deficiency did not impair synthesis or cleavage of pro-IL-1ß, but resulted in the retention of mature IL-1ß within cells. Generation of gasdermin E KO and ATG7 KO THP-1 cells revealed that the release of IL-1ß was not dependent on gasdermin E or ATG7. Collectively, our data indicate that during T. gondii Infection of human monocytes, caspase-8 functions in a novel gasdermin-independent mechanism controlling IL-1ß release from viable cells. This study expands on the molecular pathways that promote IL-1ß in human immune cells and provides evidence of a role for caspase-8 in the mechanism of IL-1ß release during infection.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Toxoplasma / Toxoplasmosis / Caspasa 8 / Interleucina-1beta Límite: Humans Idioma: En Revista: J Immunol Año: 2024 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Toxoplasma / Toxoplasmosis / Caspasa 8 / Interleucina-1beta Límite: Humans Idioma: En Revista: J Immunol Año: 2024 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Estados Unidos