Natural killer cells as an initial defense against pathogens

Lodoen, Melissa B.; Lanier, Lewis L.

doi:10.1016/j.coi.2006.05.002

Cited by 393 publications

(331 citation statements)

References 52 publications

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“…NK cells can contribute to host resistance to viruses, bacteria and certain parasites as well as providingimmune surveillance against the development of tumors (11)(12)(13). NK cells mediate their effects through cellular cytotoxicity alongside the production of a range of cytokines and other immunoregulatory mediators (14)(15)(16)(17)(18)(19).…”

mentioning

confidence: 99%

NK Cells Influence Both Innate and Adaptive Immune Responses after Mucosal Immunization with Antigen and Mucosal Adjuvant

Hall

Clare

Dougan

2010

The Journal of Immunology

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mentioning

confidence: 99%

NK Cells Influence Both Innate and Adaptive Immune Responses after Mucosal Immunization with Antigen and Mucosal Adjuvant

Hall

Clare

Dougan

2010

The Journal of Immunology

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“…NK cells are part of the innate immune system and function as both immune surveillance monitors and as effector cells against invading pathogens and developing tumours (Lodoen and Lanier, 2006). NK cells are activated by engaging highly polymorphic sets of receptors and carry out their effector functions by producing cytokines, particularly interferon-g, and by lysing cells infected with pathogens.…”

Section: Discussionmentioning

confidence: 99%

Pig peripheral blood mononuclear leucocyte subsets are heritable and genetically correlated with performance

Clapperton

Glass

Bishop

2008

Animal

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Indicator traits used to select pigs for increased resistance to infection or improved health must be heritable and, preferably, be associated with improved performance. We estimated the heritability of a range of immune traits and their genetic and phenotypic correlations with growth performance. We measured immune traits on 589 pigs and performance on 1941 pigs from six farms, three of which were classified as 'high health status' (i.e. specific pathogen-free) and three were of lower health status. All pigs were apparently healthy. Immune traits were total white blood cells (WBC), and peripheral blood mononuclear leucocyte (PBML) subsets positive for CD4, CD8a, gamma delta (gd) T cell receptor, CD11R1 (natural killer cell marker), B cell and monocyte markers at the start and the end of standard growth performance tests. At both time points, all immune traits were moderately to highly heritable except for CD8a 1 cells. At end of test, heritability estimates (h 2 ) (6s.e.) were 0.18 (60.11) for total WBC count. For PBML subset proportions, the heritabilities were 0.52 (60.14) for gd TCR 1 cells, 0.62 (60.14) for CD4 1 cells, 0.44 (60.14) for CD11R1 1 cells, 0.58 (60.14) for B cells and 0.59 (60.14) for monocytes. Farm health status affected the heritabilities for WBC, being substantially higher on lower health status farms, but did not have consistent effects on heritabilities for the PBML subsets. There were significant negative genetic correlations between numbers and proportions of various PBML subsets and performance, at both start and end of test. In particular, the proportion of PBML cells that were CD11R1 1 cells, at end of test, was strongly correlated with daily gain (r g 5 20.72; P , 0.01). There were also weaker but significant negative phenotypic correlations between PBML subsets measured at end of test and performance, for gd 1 T cells, CD8a 1 , CD11R1 1 cells, B cells or monocytes. Phenotypic correlations with daily gain were generally lower at the start of test than at the end of test. These results show that most of the major pig PBML subsets are heritable, and that systemic levels of several of these PBML subsets are genetically negatively correlated with performance. This approach provides a basis for using immune trait markers when selecting boars that can produce higher-performing progeny.

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“…The effectors of this arm of the innate response are NK cells 63 , and the TAM signalling system also has an important role in regulating the activity of these cells 22 . This regulation again appears to be carried out in concert with cytokine receptors.…”

Section: Tam Control Of Natural-killer-cell Differentiationmentioning

confidence: 99%

Immunobiology of the TAM receptors

2008

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Recent studies have revealed that the TAM receptor protein tyrosine kinases -TYRO3, AXL and MER -have pivotal roles in innate immunity. They inhibit inflammation in dendritic cells and macrophages, promote the phagocytosis of apoptotic cells and membranous organelles, and stimulate the maturation of natural killer cells. Each of these phenomena may depend on a cooperative interaction between TAM receptor and cytokine receptor signalling systems. Although its importance was previously unrecognized, TAM signalling promises to have an increasingly prominent role in studies of innate immune regulation.Receptor protein tyrosine kinases (PTKs) are cell-surface transmembrane receptors that contain a regulated PTK activity within their cytoplasmic domains. They function as sensors for extracellular ligands, the binding of which triggers receptor dimerization and activation of the receptor's kinase. This leads to the recruitment, phosphorylation and activation of multiple downstream signalling proteins, which ultimately change the physiology of cells. Although there are only 58 receptor PTK genes in the human genome 1 (see the human kinome website), the signal transduction cascades initiated by receptor PTK activation control diverse cellular processes -from cell differentiation to cell death. Well-known receptor PTK subfamilies include the ERBB receptors, which have essential roles in cardiac and neural development and the progression of some forms of breast cancer 2 ; and the ephrin receptors, which are required for tissue morphogenesis and the patterning of neuronal connections in the developing brain 3 .The focus of this Review, the TAM group, was among the last receptor PTK subfamilies to be identified, and the biological roles of its three members -TYRO3, AXL and MERremained uncharacterized for several years. Largely through the analysis of engineered lossof-function mutants in mice, these roles have become increasingly apparent. They reflect a specific requirement for TAM signalling in settings in which fully differentiated cells, tissues and organs must be maintained in the face of continuous challenge, turnover and renewal. In humans, ongoing homeostatic regulation of this sort must be carried out, frequently on a daily basis, for decades. Although an essential role for TAM regulation of tissue homeostasis is evident in the adult nervous, reproductive and vascular systems, it is in In this Review, we highlight the central roles that TAM signalling has in the intrinsic inhibition of the inflammatory response to pathogens by dendritic cells (DCs) and macrophages; during phagocytosis of apoptotic cells by these same cells; and in the maturation and killing activity of natural killer (NK) cells. We also discuss how, in many or all of these settings, TAM receptors depend on and interact with cytokine receptors. TAM receptors and ligandsThe three TAM receptors, TYRO3, AXL and MER, were identified as a distinct receptor PTK subfamily in 1991 (REFS 4,5 ). Subsequent cloning of full-length cDNAs by multiple labo...

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Natural killer cells as an initial defense against pathogens

Cited by 393 publications

References 52 publications

NK Cells Influence Both Innate and Adaptive Immune Responses after Mucosal Immunization with Antigen and Mucosal Adjuvant

NK Cells Influence Both Innate and Adaptive Immune Responses after Mucosal Immunization with Antigen and Mucosal Adjuvant

Pig peripheral blood mononuclear leucocyte subsets are heritable and genetically correlated with performance

Immunobiology of the TAM receptors

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