NK Cells and Their Role in Invasive Mold Infection

Schmidt, Stanislaw; Condorelli, Angelo Giuseppe; Koltze, Antonia; Lehrnbecher, Thomas

doi:10.3390/jof3020025

Cited by 12 publications

(9 citation statements)

References 86 publications

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“…Perforin and granulysin are responsible for the direct NK-cell cytotoxicity towards fungal pathogens, showed for A. fumigatus and R. oryzae after pretreatment of human NK cells with concanamycin A (ConA) (reviewed in ref. 11 ). However, it has not been fully elucidated to date how perforin or granulysin act together in the killing of fungi by NK cells.…”

Section: Discussionmentioning

confidence: 99%

“…NK cells form immunological synapses (IS) with their target cells, playing a pivotal role in the killing mechanism. The IS has been analyzed in detail for the interaction of NK and cancer cells 15 , but little is known for the IS formed between NK cells and Aspergillus fumigatus hyphae 11 . IS formation strongly depends on the polymerization of actin 16 and is impaired in NK cells obtained from allogeneic HSCT recipients, recovering within 180 days post-HSCT 17 .…”

Section: Introductionmentioning

confidence: 99%

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Subdiffraction-resolution fluorescence imaging of immunological synapse formation between NK cells and A. fumigatus by expansion microscopy

Trinks¹,

Reinhard²,

Drobny

et al. 2021

Commun Biol

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Expansion microscopy (ExM) enables super-resolution fluorescence imaging on standard microscopes by physical expansion of the sample. However, the investigation of interactions between different organisms such as mammalian and fungal cells by ExM remains challenging because different cell types require different expansion protocols to ensure identical, ideally isotropic expansion of both partners. Here, we introduce an ExM method that enables super-resolved visualization of the interaction between NK cells and Aspergillus fumigatus hyphae. 4-fold expansion in combination with confocal fluorescence imaging allows us to resolve details of cytoskeleton rearrangement as well as NK cells’ lytic granules triggered by contact with an RFP-expressing A. fumigatus strain. In particular, subdiffraction-resolution images show polarized degranulation upon contact formation and the presence of LAMP1 surrounding perforin at the NK cell-surface post degranulation. Our data demonstrate that optimized ExM protocols enable the investigation of immunological synapse formation between two different species with so far unmatched spatial resolution.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Subdiffraction-resolution fluorescence imaging of immunological synapse formation between NK cells and A. fumigatus by expansion microscopy

Trinks¹,

Reinhard²,

Drobny

et al. 2021

Commun Biol

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show abstract

“…Upon recognition, NK cells either induce lysis of these pathogens by secreting perforin and granulysin or trigger activation of other immune cells by releasing IFN-γ ( 60 ). Fungal pathogen-specific NK cell receptors and their mechanism of action has been reviewed ( 61 , 62 ).…”

Section: Current and Future Strategies To Control Fungal Infectionsmentioning

confidence: 99%

Methods of Controlling Invasive Fungal Infections Using CD8+ T Cells

2018

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Invasive fungal infections (IFIs) cause high rates of morbidity and mortality in immunocompromised patients. Pattern-recognition receptors present on the surfaces of innate immune cells recognize fungal pathogens and activate the first line of defense against fungal infection. The second line of defense is the adaptive immune system which involves mainly CD4+ T cells, while CD8+ T cells also play a role. CD8+ T cell-based vaccines designed to prevent IFIs are currently being investigated in clinical trials, their use could play an especially important role in acquired immune deficiency syndrome patients. So far, none of the vaccines used to treat IFI have been approved by the FDA. Here, we review current and future antifungal immunotherapy strategies involving CD8+ T cells. We highlight recent advances in the use of T cells engineered using a Sleeping Beauty vector to treat IFIs. Recent clinical trials using chimeric antigen receptor (CAR) T-cell therapy to treat patients with leukemia have shown very promising results. We hypothesized that CAR T cells could also be used to control IFI. Therefore, we designed a CAR that targets β-glucan, a sugar molecule found in most of the fungal cell walls, using the extracellular domain of Dectin-1, which binds to β-glucan. Mice treated with D-CAR+ T cells displayed reductions in hyphal growth of Aspergillus compared to the untreated group. Patients suffering from IFIs due to primary immunodeficiency, secondary immunodeficiency (e.g., HIV), or hematopoietic transplant patients may benefit from bioengineered CAR T cell therapy.

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“…As the first line of defence to eliminate infected cells and tumor cells, NK cells can produce regulatory cytokines, such as IFN- γ and GM-CSF [ 40 ]. However, in patients with TB-DM, the number of NK cells increased, which may be related to the inhibition of the expression of CD4 + T cells that promoted the proliferation of NK cells [ 41 ].…”

Section: Effect Of Hyperglycemia On Innate Immune Cells In Patients W...mentioning

confidence: 99%

Cellular Immunity of Patients with Tuberculosis Combined with Diabetes

Cheng

Wang

Gong

2022

Journal of Immunology Research

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Tuberculosis (TB) is one of humanity’s three major infectious diseases. Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia due to impaired insulin secretion or impaired insulin function. It has been reported that DM is a primary risk factor for TB disease. Given the increasing public health threat to people’s health, more and more studies have focused on diabetes complicated by TB. Hyperglycemia can affect the function of human immune cells, promote primary infections and reactivation of TB, and increase the susceptibility and severity of TB. However, the immunological mechanism behind it is still not clear. By reviewing the related articles on tuberculosis complicated with diabetes published in recent years, this paper expounds on the effect of hyperglycemia on innate immunity and adaptive immunity of patients with TB. This review provides new insights for elucidating the immunological mechanism of TB complicated with DM and lays the foundation for finding potential targets for preventing and treating TB combined with DM.

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NK Cells and Their Role in Invasive Mold Infection

Cited by 12 publications

References 86 publications

Subdiffraction-resolution fluorescence imaging of immunological synapse formation between NK cells and A. fumigatus by expansion microscopy

Subdiffraction-resolution fluorescence imaging of immunological synapse formation between NK cells and A. fumigatus by expansion microscopy

Methods of Controlling Invasive Fungal Infections Using CD8+ T Cells

Cellular Immunity of Patients with Tuberculosis Combined with Diabetes

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