10
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      IL-21-dependent expansion of memory-like NK cells enhances protective immune responses against Mycobacterium tuberculosis

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Natural killer (NK) cells are traditionally considered as innate cells but recent studies suggest that NK cells can distinguish antigens, and that memory NK cells expand and protect against viral pathogens. Limited information is available about the mechanisms involved in memory-like NK cell expansion, and their role in bacterial infections and vaccine-induced protective immune responses. In the current study, using a mouse model of tuberculosis (TB) infection, we found that IFN-γ producing CD3-NKp46+CD27+KLRG1+ memory-like NK cells develop during Bacille Calmette-Guerin (BCG) vaccination, expand and provide protection against challenge with Mycobacterium tuberculosis (M. tb). Using antibodies, siRNA and gene-deleted mice, we found that expansion of memory-like NK cells depends on IL-21. NKp46+CD27+KLRG1+ NK cells expanded in healthy individuals with latent TB infection (LTBI) in IL-21 dependent fashion. Our study provides first evidence that memory-like NK cells survive long term, expansion depends on IL-21 and involved in vaccine induced protective immunity against a bacterial pathogen.

          Related collections

          Most cited references39

          • Record: found
          • Abstract: found
          • Article: found
          Is Open Access

          The WHO 2014 Global tuberculosis report—further to go

            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            The dynamic life of natural killer cells.

            Natural killer (NK) cells play important roles in immunological processes, including early defense against viral infections. This review provides an overview of the dynamic in vivo life of NK cells from their development in the bone marrow to their mature peripheral responses and their ultimate demise, with particular emphasis on mouse NK cells and viral infections.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Preactivation with IL-12, IL-15, and IL-18 induces CD25 and a functional high-affinity IL-2 receptor on human cytokine-induced memory-like natural killer cells.

              Natural killer (NK) cells are effector lymphocytes that are under clinical investigation for the adoptive immunotherapy of hematologic malignancies, especially acute myeloid leukemia. Recent work in mice has identified innate memory-like properties of NK cells. Human NK cells also exhibit memory-like properties, and cytokine-induced memory-like (CIML) NK cells are generated via brief preactivation with IL-12, IL-15, and IL-18, which later exhibit enhanced functionality upon restimulation. However, the optimal cytokine receptors and signals for maintenance of enhanced function and homeostasis after preactivation remain unclear. Here, we show that IL-12, IL-15, and IL-18 preactivation induces a rapid and prolonged expression of CD25, resulting in a functional high-affinity IL-2 receptor (IL-2Rαβγ) that confers responsiveness to picomolar concentrations of IL-2. The expression of CD25 correlated with STAT5 phosphorylation in response to picomolar concentrations of IL-2, indicating the presence of a signal-competent IL-2Rαβγ. Furthermore, picomolar concentrations of IL-2 acted synergistically with IL-12 to costimulate IFN-γ production by preactivated NK cells, an effect that was CD25 dependent. Picomolar concentrations of IL-2 also enhanced NK cell proliferation and cytotoxicity via the IL-2Rαβγ. Further, after adoptive transfer into immunodeficient NOD-SCID-γc(-/-) mice, human cytokine-preactivated NK cells expand preferentially in response to exogenous IL-2. Collectively, these data demonstrate that human CIML NK cells respond to IL-2 via IL-2Rαβγ with enhanced survival and functionality, and they provide additional rationale for immunotherapeutic strategies that include brief cytokine preactivation before adoptive NK cell transfer, followed by low-dose IL-2 therapy.
                Bookmark

                Author and article information

                Journal
                101299742
                35518
                Mucosal Immunol
                Mucosal Immunol
                Mucosal immunology
                1933-0219
                1935-3456
                29 October 2016
                07 December 2016
                08 June 2017
                : 10.1038/mi.2016.105
                Affiliations
                [1 ]Department of Pulmonary Immunology, Center for Biomedical Research, University of Texas Health Science Center at Tyler, Tyler, Texas, 75708, USA.
                [2 ]Department of Immunology, M. D. Anderson Cancer Center, Houston, Texas, 77030, USA.
                Author notes
                Corresponding author: Ramakrishna Vankayalapati, Pulmonary Immunology, University of Texas Health Center, 11937 US Highway 271, Tyler, TX 75708-3154, telephone (903) 877-5190, fax (903) 877-7989, krishna.vankayalapati@ 123456uthct.edu
                Article
                NIHMS826155
                10.1038/mi.2016.105
                5462891
                27924822
                e85c3047-103a-436c-b061-0f961372eb17

                Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms

                History
                Categories
                Article

                Immunology
                Immunology

                Comments

                Comment on this article