Human Invariant Natural Killer T cells possess immune-modulating functions during<i>Aspergillus</i>infection

Beitzen-Heineke, Antonia; Bouzani, Maria; Schmitt, Anna-Lena; Kurzai, Oliver; Hünniger, Kerstin; Einsele, Hermann; Loeffler, Juergen

doi:10.1093/mmy/myv074

Cited by 7 publications

(4 citation statements)

References 38 publications

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“…Furthermore, CD1d-deficient mice poorly control infections with Aspergillus fumigatus ( Cohen et al., 2011 ) reflecting the need for NKT cells in the control of fungal infections. In addition, human NKT cells exhibit immunomodulatory effects following exposure to Aspergillus spp ( Beitzen-Heineke et al., 2016 ).…”

Section: Nkt Cell Antigensmentioning

confidence: 99%

NKT Cells Contribute to the Control of Microbial Infections

Vogt

Mattner

2021

Front. Cell. Infect. Microbiol.

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Innate (-like) T lymphocytes such as natural killer T (NKT) cells play a pivotal role in the recognition of microbial infections and their subsequent elimination. They frequently localize to potential sites of pathogen entry at which they survey extracellular and intracellular tissue spaces for microbial antigens. Engagement of their T cell receptors (TCRs) induces an explosive release of different cytokines and chemokines, which often pre-exist as constitutively expressed gene transcripts in NKT cells and underlie their poised effector state. Thus, NKT cells regulate immune cell migration and activation and subsequently, bridge innate and adaptive immune responses. In contrast to conventional T cells, which react to peptide antigens, NKT cells recognize lipids presented by the MHC class I like CD1d molecule on antigen presenting cells (APCs). Furthermore, each NKT cell TCR can recognize various antigen specificities, whereas a conventional T lymphocyte TCR reacts mostly only to one single antigen. These lipid antigens are either intermediates of the intracellular APC`s-own metabolism or originate from the cell wall of different bacteria, fungi or protozoan parasites. The best-characterized subset, the type 1 NKT cell subset expresses a semi-invariant TCR. In contrast, the TCR repertoire of type 2 NKT cells is diverse. Furthermore, NKT cells express a panoply of inhibitory and activating NK cell receptors (NKRs) that contribute to their primarily TCR-mediated rapid, innate like immune activation and even allow an adaption of their immune response in an adoptive like manner. Dueto their primary localization at host-environment interfaces, NKT cells are one of the first immune cells that interact with signals from different microbial pathogens. Vice versa, the mutual exchange with local commensal microbiota shapes also the biology of NKT cells, predominantly in the gastrointestinal tract. Following infection, two main signals drive the activation of NKT cells: first, cognate activation upon TCR ligation by microbial or endogenous lipid antigens; and second, bystander activation due to cytokines. Here we will discuss the role of NKT cells in the control of different microbial infections comparing pathogens expressing lipid ligands in their cell walls to infectious agents inducing endogenous lipid antigen presentation by APCs.

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Section: Nkt Cell Antigensmentioning

confidence: 99%

NKT Cells Contribute to the Control of Microbial Infections

Vogt

Mattner

2021

Front. Cell. Infect. Microbiol.

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“…Mechanistically, this report demonstrated that Dectin-1-and MyD88-dependent responses promoted IL-12 production by DCs that drove NKT cells to secrete interferon (IFN)-γ. Building upon this observation, human NKT cells were examined for their response to distinct fungal morphotypes and DCs [24] . It was shown that CD1d+ CD1c+ myeloid DCs were the most potent activator of NKT cells.…”

Section: Macrophages Inflammatory Monocytes Eosinophils and Naturamentioning

confidence: 99%

Innate Lung Defense during Invasive Aspergillosis: New Mechanisms

Garth¹,

Steele²

2017

J Innate Immun

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Invasive aspergillosis (IA) is one of the most difficult to treat and, consequently, one of the most lethal fungal infections known to man. Continued use of immunosuppressive agents during chemotherapy and organ transplantation often leads to the development of neutropenia, the primary risk factor for IA. However, IA is also becoming more appreciated in chronic diseases associated with corticosteroid therapy. The innate immune response to Aspergillus fumigatus, the primary agent in IA, plays a pivotal role in the recognition and elimination of organisms from the pulmonary system. This review highlights recent findings about innate host defense mechanisms, including novel aspects of innate cellular immunity and pathogen recognition, and the inflammatory mediators that control infection with A. fumigatus.

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“…Alveolar macrophages, neutrophils, and peripheral blood monocytes are the first line of phagocytic host anti- Aspergillus defences to inhaled conidia and hyphae [ 4 , 14 ]. Cytokine-mediated recruitment of natural killer effector cells is necessary for effective host defence against Aspergillus infection [ 15 ]. Additionally, a number of membrane-bound and soluble pathogen-recognition receptors (PRRs) that identify fungal motifs including toll-like receptors (TLRs), dectin-1, surfactant proteins A and D, mannose-binding lectin (MBL), and pentraxin-3 are important triggers of innate immune response leading to complement activation, phagocytosis, and killing of ingested fungi [ 16 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

Innate and Adaptive Immune Defects in Chronic Pulmonary Aspergillosis

Bongomin

Harris²,

Foden³

et al. 2017

JoF

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We evaluated the expression of biomarkers of innate and adaptive immune response in correlation with underlying conditions in 144 patients with chronic pulmonary aspergillosis (CPA). Patients with complete medical and radiological records, white cell counts, and a complete panel of CD3, CD4, CD8, CD19, and CD56 lymphocyte subsets were included. Eighty-four (58%) patients had lymphopenia. Six (4%) patients had lymphopenia in all five CD variables. There were 62 (43%) patients with low CD56 and 62 (43%) patients with low CD19. Ten (7%) patients had isolated CD19 lymphopenia, 18 (13%) had isolated CD56 lymphopenia, and 15 (10%) had combined CD19 and CD56 lymphopenia only. Forty-eight (33%) patients had low CD3 and 46 (32%) had low CD8 counts. Twenty-five (17%) patients had low CD4, 15 (10%) of whom had absolute CD4 counts <200/μL. Multivariable logistic regression showed associations between: low CD19 and pulmonary sarcoidosis (Odds Ratio (OR), 5.53; 95% Confidence Interval (CI), 1.43–21.33; p = 0.013), and emphysema (OR, 4.58; 95% CI; 1.36–15.38; p = 0.014), low CD56 and no bronchiectasis (OR, 0.27; 95% CI, 0.10–0.77; p = 0.014), low CD3 and both multicavitary CPA disease (OR, 2.95; 95% CI, 1.30–6.72; p = 0.010) and pulmonary sarcoidosis (OR, 4.94; 95% CI, 1.39–17.57; p = 0.014). Several subtle immune defects are found in CPA.

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Human Invariant Natural Killer T cells possess immune-modulating functions duringAspergillusinfection

Cited by 7 publications

References 38 publications

NKT Cells Contribute to the Control of Microbial Infections

NKT Cells Contribute to the Control of Microbial Infections

Innate Lung Defense during Invasive Aspergillosis: New Mechanisms

Innate and Adaptive Immune Defects in Chronic Pulmonary Aspergillosis

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