Lack of the programmed death‐1 receptor renders host susceptible to enteric microbial infection through impairing the production of the mucosal natural killer cell effector molecules. Issue 3 (14th October 2015)

• Record Type: Journal Article
• Authors: Solaymani‐Mohammadi, Shahram; Lakhdari, Omar; Minev, Ivelina; Shenouda, Steve; Frey, Blake F.; Billeskov, Rolf; Singer, Steven M.; Berzofsky, Jay A.; Eckmann, Lars; Kagnoff, Martin F.
• Is Part Of: Journal of leukocyte biology. Volume 99:Issue 3(2016)
• Page Start: 475
• Page End: 482
• Publication Date: 2015-10-14
• Subjects: Citrobacter rodentium -- granzyme B -- perforin -- attaching/effacing bacteria -- PD‐1; Leucocytes -- Periodicals; Reticulo-endothelial system -- Periodicals; 571.96
• DOI: 10.1189/jlb.4A0115-003RR
• Languages: English
• ISSNs: 0741-5400

Abstract

Abstract : PD‐1 is required for the optimal expression and production of effector molecules by conventional NK cells following gut infection. Abstract : The programmed death‐1 receptor is expressed on a wide range of immune effector cells, including T cells, natural killer T cells, dendritic cells, macrophages, and natural killer cells. In malignancies and chronic viral infections, increased expression of programmed death‐1 by T cells is generally associated with a poor prognosis. However, its role in early host microbial defense at the intestinal mucosa is not well understood. We report that programmed death‐1 expression is increased on conventional natural killer cells but not on CD4 +, CD8 + or natural killer T cells, or CD11b + or CD11c + macrophages or dendritic cells after infection with the mouse pathogen Citrobacter rodentium . Mice genetically deficient in programmed death‐1 or treated with anti–programmed death‐1 antibody were more susceptible to acute enteric and systemic infection with Citrobacter rodentium . Wild‐type but not programmed death‐1–deficient mice infected with Citrobacter rodentium showed significantly increased expression of the conventional mucosal NK cell effector molecules granzyme B and perforin. In contrast, natural killer cells from programmed death‐1–deficient mice had impaired expression of those mediators. Consistent with programmed death‐1 being important for intracellular expression of natural killer cell effector molecules, mice depleted of natural killer cells and perforin‐deficient mice manifested increased susceptibility to acute enteric infection with Citrobacter rodentium . Our findings suggest that increased programmed death‐1 signaling pathway expression by conventional natural killer cells promotes host protection at the intestinal mucosa during acute infection with a bacterial gut pathogen by enhancing the expression and production of important effectors of natural killer cell function.