Natural killer (NK) cells in antibacterial innate immunity: angels or devils?

Institut Pasteur, Cytokines and Inflammation Unit, Department of Infection and Epidemiology, Paris, France.
Molecular Medicine (Impact Factor: 4.82). 11/2011; 18(1):270-85. DOI: 10.2119/molmed.2011.00201
Source: PubMed

ABSTRACT Natural killer (NK) cells were first described as immune leukocytes that could kill tumor cells and soon after were reported to kill virus-infected cells. In the mid-1980s, 10 years after their discovery, NK cells were also demonstrated to contribute to the fight against bacterial infection, particularly because of crosstalk with other leukocytes. A wide variety of immune cells are now recognized to interact with NK cells through the production of cytokines such as interleukin (IL)-2, IL-12, IL-15 and IL-18, which boost NK cell activities. The recent demonstration that NK cells express pattern recognition receptors, namely Toll-like and nucleotide oligomerization domain (NOD)-like receptors, led to the understanding that these cells are not only under the control of accessory cells, but can be directly involved in the antibacterial response thanks to their capacity to recognize pathogen-associated molecular patterns. Interferon (IFN)-γ is the predominant cytokine produced by activated NK cells. IFN-γ is a key contributor to antibacterial immune defense. However, in synergy with other inflammatory cytokines, IFN-γ can also lead to deleterious effects similar to those observed during sepsis. Accordingly, as the main source of IFN-γ in the early phase of infection, NK cells display both beneficial and deleterious effects, depending on the circumstances.

  • Source
    • "Furthermore, NK cells are probably directly involved in the antibacterial response of the innate immune system due to their capacity to recognize pathogen-associated molecular patterns [89]. It is possible that all NK cell subsets are not equivalent in their antibacterial activity [90]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Sepsis is a systemic inflammatory response syndrome due to infection. The incidence rate is estimated to be up to 19 million cases worldwide per year and the number of cases is rising. Infection triggers a complex and prolonged host response, in which both the innate and adaptive immune response are involved. The disturbance of immune system cells plays a key role in the induction of abnormal levels of immunoregulatory molecules. Furthermore, the involvement of effector immune system cells also impairs the host response to the infective agents and tissue damage. Recently, postmortem studies of patients who died of sepsis have provided important insights into why septic patients die and showed an extensive depletion of CD4 and CD8 lymphocytes and they found that circulating blood cells showed similar findings. Thus, the knowledge of the characterization of circulating lymphocyte abnormalities is relevant for the understanding of the sepsis pathophysiology. In addition, monitoring the immune response in sepsis, including circulating lymphocyte subsets count, appears to be potential biomarker for predicting the clinical outcome of the patient. This paper analyzes the lymphocyte involvement and dysfunction found in patients with sepsis and new opportunities to prevent sepsis and guide therapeutic intervention have been revealed.
    BioMed Research International 08/2014; 2014:671087. DOI:10.1155/2014/671087 · 2.71 Impact Factor
  • Source
    • "Unlike CD4 and CD8 T cells NK cells as well as CD56+CD3+ NKT cells constitutively express TLR 1–8 with high expression of TLR2 and 3 at mRNA level. They recognize bacterial PAMPs and respond by producing α-defensins (108–111). Human NK cells can also directly recognize Mycobacterium bovis via TLR2 and enhance their cytolytic activity against tumor cells (112). Tumor-associated macrophages induce NK cell IFN-γ production and cytolytic activity upon TLR engagement (113). "
    [Show abstract] [Hide abstract]
    ABSTRACT: The tumor microenvironment is an important aspect of cancer biology that contributes to tumor initiation, tumor progression and responses to therapy. The composition and charac-teristics of the tumor microenvironment vary widely and are important in determining the anti-tumor immune response. Successful immunization requires activation of both innate and adaptive immunity. Generally, immune system is compromised in patients with can-cer due to immune suppression, loss of tumor antigen expression and dysfunction of antigen presenting cells (APC). Thus, therapeutic immunization leading to cancer regres-sion remains a significant challenge. Certain cells of the immune system, including dendritic cells (DCs) and gamma delta (γδ)T cells are capable of driving potent anti-tumor responses. The property of MHC-unrestricted cytotoxicity, high potential of cytokine release, tissue tropism and early activation in infections and malignant disease makes γδ T cells as an emerging candidate for immunotherapy. Various strategies are being developed to enhance anti-tumor immune responses of γδ T cells and DCs one of them is the use of novel adju-vants like toll like receptors (TLR) agonists, which enhance γδ T cell function directly or through DC activation, which has ability to prime γδ T cells. TLR agonists are being used clinically either alone or in combination with tumor antigens and has shown initial success in both enhancing immune responses and eliciting anti-tumor activity. TLR activated γδ T cells and DCs nurture each other's activation. This provides a potent base for first line of defense and manipulation of the adaptive response against pathogens and cancer. The available data provides a strong rationale for initiating combinatorial therapy for the treat-ment of diseases and this review will summarize the application of adjuvants (TLRs) for boosting immune response of γδ T cells to treat cancer and infectious diseases and their use in combinatorial therapy.
    Frontiers in Immunology 07/2014; 5(366):1-12. DOI:10.3389/fimmu.2014.00366
  • Source
    • "Pobudza fagocytozę i uwalnianie cytokin przez granulocyty . Szczególna rola IL-15 w patologii płuc polega na stymulowaniu dojrzewania i różnicowania NKC, które są niezbędnym elementem wczesnej wrodzonej odpowiedzi immunologicznej na zakażenie [30]. Wiąże się to sRAGE jedynie w BALF, co sugeruje że tkanka płucna była głównym źródłem zwiększonej ekspresji receptora [32]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The early organism response to injury or infection involves activation of the innate immune system, in which pattern recognition receptors (PRRs) participate. They recognize highly conservative structures that are called pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). The interactions between PRRs and PAMPs or DAMPs lead to the activation of transcriptional factors which are responsible for gene expression of inflammatory mediators and synthesis and release of these factors, and result in the development of inflammation. RAGE (receptor for advanced glycation end products) and CD163 belonging to PRRs play a significant role in the early immune response in lungs. They are expressed on alveolar epithelial cells and alveolar macrophages, respectively. NK cells are also involved in lung response to injury, though their maturation and the ability to express PRRs depend on the presence of IL-15. Detailed knowledge about these factors enables us to understand the signal pathways that are activated in the course of infectious and noninfectious lung injury. The analysis of these proteins' concentrations in body fluids creates new possibilities in monitoring lung injury and predicting the results of treatment. In the future, the discussed mediators may become the targets for new forms of treatment in life-threatening respiratory diseases.
Show more