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.