[PMID]: | 29180487 |
[Au] Autor: | Pierog PL; Zhao Y; Singh S; Dai J; Yap GS; Fitzgerald-Bocarsly P |
[Ad] Endereço: | Department of Pathology and Laboratory Medicine, Rutgers New Jersey Medical School, Newark, NJ 07103. |
[Ti] Título: | Inactivates Human Plasmacytoid Dendritic Cells by Functional Mimicry of IL-10. |
[So] Source: | J Immunol;200(1):186-195, 2018 01 01. |
[Is] ISSN: | 1550-6606 |
[Cp] País de publicação: | United States |
[La] Idioma: | eng |
[Ab] Resumo: | Plasmacytoid dendritic cells (pDCs) are the major producers of IFN-α, an antiviral cytokine involved in immunomodulation and control of HIV type 1 replication, whereas is a life-threatening opportunistic infection in AIDS patients. During infection with HIV type 1, human pDCs decrease in circulation and remaining pDC produce lower amounts of IFN-α in response to viral stimulation. In this study, we investigated the impact of coinfection with on the innate virus-directed responses of human pDCs. Using intracellular flow cytometry and fluorescence microscopy, we determined that invaded but did not induce IFN-α or TNF-α in human pDC. However, inhibited IFN-α and TNF-α produced in response to HSV and HIV, thus functionally inactivating pDC. IFN-α production was inhibited only in cells infected by , which inhibited neither uptake of GFP-HSV nor localization of TLR9 in CD71 endosomes, directing us to investigate downstream events. Using imaging flow cytometry, we found that both and IL-10 inhibited virus-induced nuclear translocation, but not phosphorylation, of IFN response factor 7. Blockade of IFN response factor 7 nuclear translocation and inhibition of the IFN-α response was partially reversed by a deficiency in the -derived ROP16 kinase, known to directly phosphorylate STAT3, a critical mediator of IL-10's anti-inflammatory effects. Taken together, our results indicate that suppresses pDC activation by mimicking IL-10's regulatory effects through an ROP16 kinase-dependent mechanism. Our findings further imply a convergent mechanism of inhibition of TLR signaling by and IL-10 and suggest potential negative consequences of HIV/ coinfection. |
[Mh] Termos MeSH primário: |
Células Dendríticas/imunologia Infecções por HIV/imunologia HIV-1/imunologia Interleucina-10/metabolismo Infecções Oportunistas/imunologia Proteínas Tirosina Quinases/metabolismo Proteínas de Protozoários/metabolismo Toxoplasma/imunologia Toxoplasmose/imunologia
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[Mh] Termos MeSH secundário: |
Diferenciação Celular Células Cultivadas Coinfecção Células Dendríticas/parasitologia Seres Humanos Imunidade Inata Imunomodulação Fator Regulador 7 de Interferon/metabolismo Interferon-alfa/metabolismo Fator de Transcrição STAT3/metabolismo Transdução de Sinais Receptor Toll-Like 9/metabolismo Fator de Necrose Tumoral alfa/metabolismo
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[Pt] Tipo de publicação: | JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, N.I.H., EXTRAMURAL |
[Nm] Nome de substância:
| 0 (IRF7 protein, human); 0 (Interferon Regulatory Factor-7); 0 (Interferon-alpha); 0 (Protozoan Proteins); 0 (STAT3 Transcription Factor); 0 (Toll-Like Receptor 9); 0 (Tumor Necrosis Factor-alpha); 130068-27-8 (Interleukin-10); EC 2.7.10.1 (Protein-Tyrosine Kinases); EC 2.7.10.1 (Rop16 protein, Toxoplasma gondii) |
[Em] Mês de entrada: | 1801 |
[Cu] Atualização por classe: | 180307 |
[Lr] Data última revisão:
| 180307 |
[Sb] Subgrupo de revista: | AIM; IM |
[Da] Data de entrada para processamento: | 171129 |
[St] Status: | MEDLINE |
[do] DOI: | 10.4049/jimmunol.1701045 |
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