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Immunohorizons ; 8(4): 355-362, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38687282

RESUMO

To defend against intracellular pathogens such as Toxoplasma gondii, the host generates a robust type 1 immune response. Specifically, host defense against T. gondii is defined by an IL-12-dependent IFN-γ response that is critical for host resistance. Previously, we demonstrated that host resistance is mediated by T-bet-dependent ILC-derived IFN-γ by maintaining IRF8+ conventional type 1 dendritic cells during parasitic infection. Therefore, we hypothesized that innate lymphoid cells are indispensable for host survival. Surprisingly, we observed that T-bet-deficient mice succumb to infection quicker than do mice lacking lymphocytes, suggesting an unknown T-bet-dependent-mediated host defense pathway. Analysis of parasite-mediated inflammatory myeloid cells revealed a novel subpopulation of T-bet+ myeloid cells (TMCs). Our results reveal that TMCs have the largest intracellular parasite burden compared with other professional phagocytes, suggesting they are associated with active killing of T. gondii. Mechanistically, we established that IL-12 is necessary for the induction of inflammatory TMCs during infection and these cells are linked to a role in host survival.


Assuntos
Interleucina-12 , Camundongos Endogâmicos C57BL , Camundongos Knockout , Células Mieloides , Proteínas com Domínio T , Toxoplasma , Toxoplasmose , Animais , Toxoplasma/imunologia , Camundongos , Interleucina-12/metabolismo , Interleucina-12/imunologia , Proteínas com Domínio T/metabolismo , Proteínas com Domínio T/genética , Proteínas com Domínio T/imunologia , Células Mieloides/imunologia , Células Mieloides/metabolismo , Toxoplasmose/imunologia , Toxoplasmose/parasitologia , Interferon gama/metabolismo , Interferon gama/imunologia , Imunidade Inata , Toxoplasmose Animal/imunologia , Resistência à Doença/imunologia , Feminino
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