Human NK cells adapt their immune response towards increasing multiplicities of infection of Aspergillus fumigatus

Marischen, Lothar; Englert, Anne; Schmitt, Anna-Lena; Einsele, Hermann; Loeffler, Juergen

doi:10.1186/s12865-018-0276-6

Cited by 14 publications

(15 citation statements)

References 68 publications

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“… 8 , 9 On observing that these cells were able to spontaneously kill syngeneic and allogeneic tumor cells without the requirement of prior sensitization or affinity maturation, they were named “natural killers”. 2 , 10 , 11 Since then, they have gained enormous interest from researchers due to their successful utilization in immunotherapy. This review aims to summarize the established and emerging knowledge to broaden our current understanding of human NK cells.…”

Section: Human Nk Cells – From Development To Effector Functionsmentioning

confidence: 99%

Human NK cells: From development to effector functions

Arachchige

2021

Innate Immun

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NK cells are the major lymphocyte subset of the innate immune system that mediates antiviral and anti-tumor responses. It is well established that they develop mechanisms to distinguish self from non-self during the process of NK cell education. Unlike T and B cells, natural killer cells lack clonotypic receptors and are activated after recognizing their target via germline-encoded receptors through natural cytotoxicity, cytokine stimulation, and Ab-dependent cellular cytotoxicity. Subsequently, they utilize cytotoxic granules, death receptor ligands, and cytokines to perform their effector functions. In this review, we provide a general overview of human NK cells, as opposed to murine NK cells, discussing their ontogeny, maturation, receptor diversity, types of responses, and effector functions. Furthermore, we also describe recent advances in human NK cell biology, including tissue-resident NK cell populations, NK cell memory, and novel approaches used to target NK cells in cancer immunotherapy.

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Section: Human Nk Cells – From Development To Effector Functionsmentioning

confidence: 99%

Human NK cells: From development to effector functions

Arachchige

2021

Innate Immun

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“…28 Furthermore, chemokines have been detected to be released earlier than cytokines (TNF-α and IFN-γ), which indicates that recruitment of macrophages and neutrophils by NK cells is in advance of adaptive immunity by cytokines when counteracting a fungal infection. 27 IL-10 is the cytokine with the highest AUC (0.792, 95% CI: 0.651-0.889) in our study. IL-10 is released from macrophages and DCs, and the main capacity of this anti-inflammatory cytokine is to block production of other cytokines from T helper (Th)1 cells.…”

Section: Ta B L E 5 Diagnostic Parameters Of Cytokines and Chemokinesmentioning

confidence: 50%

“…In addition, functions and recruitment of NK cells are mediated by chemokines including MIP‐1α and MIP‐1β during fungal infections . For example, during A fumigatus infections, MIP‐1α and MIP‐1β are prominently up‐regulated in NK cells . In particular, MIP‐1 is regarded as a critical mediator of host defense against A fumigatus infection and its single nucleotide polymorphisms are significantly correlated with fungal infections .…”

Section: Discussionmentioning

confidence: 99%

“…25,26 For example, during A fumigatus infections, MIP-1α and MIP-1β are prominently up-regulated in NK cells. 27 In particular, MIP-1 is regarded as a critical mediator of host defense against A fumigatus infection and its single nucleotide polymorphisms are significantly correlated with fungal infections. 28 Furthermore, chemokines have been detected to be released earlier than cytokines (TNF-α and IFN-γ), which indicates that recruitment of macrophages and neutrophils by NK cells is in advance of adaptive immunity by cytokines when counteracting a fungal infection.…”

Section: Ta B L E 5 Diagnostic Parameters Of Cytokines and Chemokinesmentioning

confidence: 99%

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Diagnostic efficacy of serum cytokines and chemokines in fungal bloodstream infection in febrile patients

Wang

Yang

Wang

et al. 2020

Clinical Laboratory Analysis

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Background:The role of serum cytokines/chemokines in early diagnosis of fungal infections has not been clearly clarified yet. This study aims to measure the serum levels of cytokines/chemokines in cases of fungemia and to compare them with culture-negative controls. Methods:In total, fourteen types of serum cytokines and chemokines from 41 patients with fungemia were compared with 57 patients with negative blood culture results. The cytokine and chemokine levels were detected with multiplex platform.We then performed statistical analysis as a two-tailed P < .05. ROC analysis was performed, and an area under the curve (AUC), and sensitivity and specificity values were calculated to determine the efficacy of various cytokines and chemokines for fungemia. Binary logistic regression was performed to further explore the combination mode of cytokines and chemokines, which could increase the diagnostic efficiency.Results: C-reactive protein and procalcitonin were significantly higher compared with those in negative control group, while white blood cell, percentage of neutrophil, percentage of lymphocyte, and ratio of neutrophil and lymphocyte did not differentiate between two groups. Serum levels of IFN-γ, TNF-α, MIP-1β, IL-6, IL-8, IL-10, IL-12p70, and IL-17 were significantly higher in patients with fungemia compared with the control group. Combination of MIP-1β and IL-17 could improve the AUC, sensitivity, and specificity for the diagnosis of fungemia. Conclusion:Our study demonstrates that serum cytokines and chemokines including IFN-γ, TNF-α, MIP-1β, IL-6, IL-8, IL-10, IL-12p70, and IL-17 could be considered as diagnostic markers for fungemia. Combination of these biomarkers might improve the diagnostic efficiency of fungemia. Diagnostic efficacy of serum cytokines and chemokines in fungal bloodstream infection in febrile patients.

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“…GAPDH: Forward-ACC ACA GTC CAT GCC ATC AC; Reverse-TCC ACC ACC CTG TTG CTG; PD-1: Forward-AAG GCG CAG ATC AAA GAG AGC C; Reverse-CAA CCA CCA GGG TTT GGA ACT G; IL-2 (human): Forward-GTT GTT TCA GAT CCC TTT AGT TCC A; Reverse-ACA GAA CTG AAA CAT CTT CAG TGT C ; 47 CCL4 (human): Forward-GCT TCC TCG CAA CTT TGT GG; Reverse-GCG GAG AGG AGT CCT GAG TA ; 48 GZMB (human): Forward-GCA GGA AGA TCG AAA GTG CG; Reverse-TAC AGC GGG GGC TTA GTT TG ; 49 TNFA (human): Forward-AGC CCA TGT TGT AGC AAA CC; Reverse-GGA AGA CCC CTC CCA GAT AG ; 50 IFNG (human): Forward-GAA AAG CTG ACT AAT TAT TCG GTA ACT G; Reverse-GTT CAG CCA TCA CTT GGA TGA G. 51…”

Section: Real-time Quantitative Pcr Assaymentioning

confidence: 99%

Small-molecule PD-L1 inhibitor BMS1166 abrogates the function of PD-L1 by blocking its ER export

Chen

et al. 2020

OncoImmunology

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Therapeutic monoclonal antibodies against the PD-L1/PD-1 (programmed death ligand-1/programmed cell death protein-1) axis have achieved great successes in cancer treatments, but the development of smallmolecule immunomodulators of the pathway has lagged far behind. We established a cellular coculture assay with two stable transfectant cell lines, a PD-L1-expressing tumor cell line PC9/PD-L1 and a PD-1-expressing T cell line Jurkat/PD-1. Western blotting analyses were used to monitor the PD-L1/PD-1 interaction and signaling. We analyzed PD-L1 glycosylation by lectin binding assay and glycosidase digestion, and examined subcellular localization of PD-L1 by immunocytochemical staining. Luciferase assay and real-time PCR were used to evaluate T cell activation in the coculture experiments. We found that coculturing of the PC9/PD-L1 cells with the Jurkat/PD-1 cells induced a lysosomal degradation of PD-1. A smallmolecule PD-L1 inhibitor BMS1166 developed by Bristol-Myers Squibb inhibited the coculture-induced PD-1 degradation through a unique mechanism. BMS1166 specifically affected PD-L1 glycosylation and prevented transporting of the under-glycosylated form of PD-L1 from endoplasmic reticulum (ER) to Golgi, leading to accumulation of PD-L1 in ER. In doing so, BMS1166 blocked PD-L1/PD-1 signaling. Coculturing PD-L1-expressing cells with PD-1-expressing cells induced degradation of PD-1, which could be used as a readout to identify inhibitors of PD-L1/PD-1 signaling. The small-molecule PD-L1 inhibitor BMS1166 abolished the glycosylation and maturation of PD-L1 by blocking its exporting from ER to Golgi. Our study discovered a new strategy to identify inhibitors of the PD-L1/PD-1 signaling pathway and to develop new drugs for the treatment of cancer.

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Human NK cells adapt their immune response towards increasing multiplicities of infection of Aspergillus fumigatus

Cited by 14 publications

References 68 publications

Human NK cells: From development to effector functions

Human NK cells: From development to effector functions

Diagnostic efficacy of serum cytokines and chemokines in fungal bloodstream infection in febrile patients

Small-molecule PD-L1 inhibitor BMS1166 abrogates the function of PD-L1 by blocking its ER export

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