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The role of NKT cells during microbial infection

The picture depicts during infection the reciprocal activation of the NKT cell with the APC by lipid antigens and pro-inflammatory cytokines in order to activate members of the innate and adaptive immune system, including macrophages, neutrophils, B cells, NK cells, dentritic cells, and other T cells. The cell products of these activated NKT cells that serve to activate other immune cells include IFNγ, IL-4, IL-13, IL-17A, as well as other chemokines and cytokines.

FIGURE 6 | iNKT cells during microbial infection.

The figure shows a summary of the aspects of invariant natural killer T (iNKT) cell biology that determine the influence of these cells on the immune response during infection with Streptococcus pneumoniae. a | iNKT cells are selected in the thymus by self lipid antigens presented on CD1d by double-positive (DP) thymocytes. As a result of positive selection, iNKT cells express the transcription factor promyelocytic leukaemia zinc finger protein (PLZF) and leave the thymus as 'poised effectors'. b | iNKT cells exhibit subset-specific tissue distribution patterns that contribute to their functional potential. The homing and tissue retention of iNKT cell subsets is controlled in part by adhesion receptors, such as lymphocyte function-associated antigen 1 (LFA1), and also by chemokines, such as CXC-chemokine ligand 16 (CXCL16), and is regulated in part during early life by the commensal microflora. In addition to the existence of tissue-resident iNKT cells, other iNKT cells can be recruited to the tissues during immune responses. c | Following exposure to a microorganism such as S. pneumoniae, an antigen-presenting cell (APC) can present both self and foreign lipid antigens. The activation of APCs by microbial products leads to the production of self lipid antigens and pro-inflammatory cytokines such as interleukin-12 (IL-12). Lipid antigens and pro-inflammatory cytokines mediate the reciprocal activation of iNKT cells and APCs, as described in Fig. 5. d | Activated iNKT cells produce interferon-γ (IFNγ), IL-4, IL-13, IL-17A, other cytokines and chemokines, all of which promote the recruitment and activation of both innate and adaptive immune cell types. Cytokines produced by the reciprocal activation of iNKT cells and dendritic cells can transactivate other innate immune cell types, including macrophages. e | Innate immune cells such as macrophages and neutrophils that have been recruited by iNKT cell-derived cytokines and chemokines promote the early innate clearance of the pathogen. APCs that have been activated through their interactions with iNKT cells, including by CD40–CD40 ligand (CD40L) interactions, initiate antigen-specific adaptive lymphocyte responses and protective immunity. IFNGR, IFNγ receptor; IL-12R, IL-12 receptor; PRR, pattern-recognition receptor; TCR, T cell receptor.[1]

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<pubmed>23334244</pubmed> Nature Reviews Immunology

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Citation: Brennan PJ, Brigl M, Brenner MB. (2013) nvariant natural killer T cells: an innate activation scheme linked to diverse effector functions. NATURE REVIEWS IMMUNOLOGY 13(2):101-17. doi: 10.1038/nri3369. Epub 2013 Jan 21.

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Reprinted by permission from Macmillan Publishers Ltd: [Nature Reviews Immunology] (Patrick J. Brennan, Manfred Brigl & Michael B. Brenner (2013) nvariant natural killer T cells: an innate activation scheme linked to diverse effector functions. NATURE REVIEWS IMMUNOLOGY 13(2):101-17. doi: 10.1038/nri3369. Epub 2013 Jan 21., copyright (2013)

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