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

Shahram Solaymani-Mohammadi, Omar Lakhdari, Ivelina Minev, Steve Shenouda, Blake F. Frey, Rolf Billeskov, Steven M. Singer, Jay A. Berzofsky, Lars Eckmann, Martin F. Kagnoff

Research output: Contribution to journalArticle

7 Citations (Scopus)

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 withCitrobacter 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.

Original languageEnglish
Pages (from-to)475-482
Number of pages8
JournalJournal of Leukocyte Biology
Volume99
Issue number3
DOIs
Publication statusPublished - 1 Mar 2016

Keywords

  • Attaching/effacing bacteria
  • Citrobacter rodentium
  • Granzyme B
  • PD-1
  • Perforin

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