Salmonella impairs CD8 T cell response through PD-1: PD-L axis

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• 作者：Marcela Ló ; pez-Medina^a ; Ismael Carrillo-Martí ; n^a ; Jessica Leyva-Rangel^a ; ^b ; Celia Alpuche-Aranda^c ; Vianney Ortiz-Navarrete^a ; ^{vortiz@cinvestav.mx" class="auth_mail" title="E-mail the corresponding author}
• 关键词：APC ; antigen-presenting cell ; CFU ; colony-forming unit ; FACS ; fluorescence-activated cell sorter ; FITC ; fluorescein isothiocyanate ; IFN ; interferon ; IL ; interleukin ; i.p. ; intraperitoneal ; i.v. ; intravenous ; mAb ; monoclonal Ab ; MHC ; major histocompatibility complex ; OVA ; ovalbumin ; PD-1 ; programmed cell death 1 ; PD-L ; programmed cell death 1 ligand ; PE ; phycoerythrin ; TCR ; T cell receptor for Ag ; TLR ; toll-like receptor ; TNF ; tumor necrosis factor
• 刊名：Immunobiology
• 出版年：2015
• 出版时间：December 2015
• 年：2015
• 卷：220
• 期：12
• 页码：1369-1380
• 全文大小：2525 K

文摘

We have shown that Salmonella remains for a long period of time within B cells, plasma cells, and bone marrow B cell precursors, which might allow persistence and dissemination of infection. Nonetheless, how infected cells evade CD8 T cell response has not been characterized. Evidence indicates that some pathogens exploit the PD-1: PD-L (PD-L1 and PD-L2) interaction to inhibit CD8 T cells response to contribute the chronicity of the infection. To determine whether the PD-1: PD-L axis plays a role during Salmonella infection; we evaluated PD-1 expression in antigen-specific CD8 T cells and PD-1 ligands in Salmonella-infected cells. Our results show that infected B cells and macrophages express continuously co-stimulatory (CD40, CD80, and CD86) and inhibitory molecules (PD-L1 and PD-L2) in early and late stages of chronic Salmonella infection, while antigen-specific CD8 T cells express in a sustained manner PD-1 in the late stages of infection. Blocking this axis restores the ability of the CD8 T cells to proliferate and eliminate primary infected APCs. Therefore, a continuous PD-1: PDL interaction might be a mechanism employed by Salmonella to negatively regulate Salmonella-specific CD8 T cell cytotoxic response in order to remain within the host for a long period of time.