scholarly journals Enhanced Proinflammatory Cytokine Production and Immunometabolic Impairment of NK Cells Exposed to Mycobacterium tuberculosis and Cigarette Smoke

2022 ◽  
Vol 11 ◽  
Author(s):  
Yafei Rao ◽  
Xiaoyan Gai ◽  
Yanqing Le ◽  
Jing Xiong ◽  
Yujia Liu ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Oxidative Phosphorylation ◽  
Nk Cells ◽  
Cigarette Smoke ◽  
Proinflammatory Cytokine ◽  
Cytokine Production ◽  
Nk Cell ◽  
Proinflammatory Cytokine Production ◽  
Cell Subpopulations

AimSmoker COPD patients with chest radiological signs of prior tuberculosis (TB) showed more severe lung damage, but the mechanisms remain unclear. Emerging evidence has implicated NK cells in the pathogenesis of both COPD and TB. The purpose of this study was to delineate the profile and cytokine production of NK-cell subpopulations and their immunometabolic changes after exposure to both cigarette smoke (CS) and Mycobacterium tuberculosis(MTB).MethodsWe profiled NK-cell subpopulations in terms of percentage and cytokine production by flow cytometry in smoker patients with pulmonary TB (PTB). In an in vitro coexposure model, we investigated proinflammatory cytokine production, glycolytic influx, and oxidative phosphorylation of NK cells under CS extract (CSE) and PPD costimulation.ResultsPeripheral blood NK cells in smoker patients with active PTB (CS+PTB group) showed altered proportion of subpopulations and excessive proinflammatory cytokine expressions. In vitro, CSE- and PPD-coexposed NK-92 cells displayed enhanced proinflammatory cytokine production, concurrent with decreased glycolytic influx and oxidative phosphorylation.ConclusionSmoker patients with active PTB showed enhanced proinflammatory cytokine expression within altered NK cell subpopulations. CSE and PPD coexposure induced heightened cytokine production concurrent with impaired cell metabolism in NK cells. These novel data suggest a potential role of NK cells in the pathogenesis of lung injury in subjects with coexposure to CS and TB.

scholarly journals CD33 Delineates Two Functionally Distinct NK Cell Populations Divergent in Cytokine Production and Antibody-Mediated Cellular Cytotoxicity

2022 ◽  
Vol 12 ◽  
Author(s):  
Maryam Hejazi ◽  
Congcong Zhang ◽  
Sabrina B. Bennstein ◽  
Vera Balz ◽  
Sarah B. Reusing ◽  
...  
Keyword(s):  
Nk Cells ◽  
Cytokine Production ◽  
Nk Cell ◽  
Functional Divergence ◽  
Target Cells ◽  
Cellular Cytotoxicity ◽  
Transcriptional Signature ◽  
Promising Target

The generation and expansion of functionally competent NK cells in vitro is of great interest for their application in immunotherapy of cancer. Since CD33 constitutes a promising target for immunotherapy of myeloid malignancies, NK cells expressing a CD33-specific chimeric antigen receptor (CAR) were generated. Unexpectedly, we noted that CD33-CAR NK cells could not be efficiently expanded in vitro due to a fratricide-like process in which CD33-CAR NK cells killed other CD33-CAR NK cells that had upregulated CD33 in culture. This upregulation was dependent on the stimulation protocol and encompassed up to 50% of NK cells including CD56dim NK cells that do generally not express CD33 in vivo. RNAseq analysis revealed that upregulation of CD33+ NK cells was accompanied by a unique transcriptional signature combining features of canonical CD56bright (CD117high, CD16low) and CD56dim NK cells (high expression of granzyme B and perforin). CD33+ NK cells exhibited significantly higher mobilization of cytotoxic granula and comparable levels of cytotoxicity against different leukemic target cells compared to the CD33− subset. Moreover, CD33+ NK cells showed superior production of IFNγ and TNFα, whereas CD33− NK cells exerted increased antibody-dependent cellular cytotoxicity (ADCC). In summary, the study delineates a novel functional divergence between NK cell subsets upon in vitro stimulation that is marked by CD33 expression. By choosing suitable stimulation protocols, it is possible to preferentially generate CD33+ NK cells combining efficient target cell killing and cytokine production, or alternatively CD33− NK cells, which produce less cytokines but are more efficient in antibody-dependent applications.

scholarly journals Human Natural Killer Cells Mediate Killing of Intracellular Mycobacterium tuberculosis H37Rv via Granule-Independent Mechanisms

2001 ◽  
Vol 69 (3) ◽  
pp. 1755-1765 ◽  
Author(s):  
Kevin J. Brill ◽  
Qing Li ◽  
Rhonda Larkin ◽  
David H. Canaday ◽  
David R. Kaplan ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Nk Cells ◽  
Natural Killer ◽  
Nk Cell ◽  
Human Lymphocytes ◽  
Peripheral Blood Lymphocytes ◽  
Cell Contact ◽  
Mycobacterium Tuberculosis H37rv ◽  
Induced Apoptosis

ABSTRACT Despite the continued importance of tuberculosis as a world-wide threat to public health, little is known about the mechanisms used by human lymphocytes to contain and kill the intracellular pathogenMycobacterium tuberculosis. We previously described an in vitro model of infection of human monocytes (MN) with virulent M. tuberculosis strain H37Rv in which the ability of peripheral blood lymphocytes to limit intracellular growth of the organism could be measured. In the current study, we determined that lymphocyte-mediated killing of intracellular M. tuberculosis occurs within the first 24 h of coculture with infected MN. Natural killer (NK) cells isolated from both purified protein derivative (PPD)-positive and PPD-negative subjects were capable of mediating this early killing of intracellular H37Rv. NK cell-mediated killing of intracellular M. tuberculosis was not associated with the production of gamma interferon. Transferred supernatants of cocultured NK cells and M. tuberculosis-infected MN could not mediate the killing of intracellular M. tuberculosis, and Transwell studies indicated that direct cell-to-cell contact was required for NK cells to mediate the killing of the organism. Killing was not dependent upon exocytosis of NK cell cytotoxic granules. NK cells induced apoptosis of mycobacterium-infected MN, but neither killing of intracellularM. tuberculosis by NK cells nor NK cell-induced apoptosis of infected MN was inhibited by blocking the interaction of FasL and Fas. Thus, human NK cells may mediate killing of intracellular M. tuberculosis via alternative apoptotic pathways.

Unique progenitors in mouse lymph node develop into CD127+ NK cells: thymus-dependent and thymus-independent pathways

Blood ◽  
2011 ◽  
Vol 117 (15) ◽  
pp. 4012-4021 ◽  
Author(s):  
Claudia Luther ◽  
Kathrin Warner ◽  
Fumio Takei
Keyword(s):  
Lymph Node ◽  
Nk Cells ◽  
Normal Mouse ◽  
Cytokine Production ◽  
Nk Cell ◽  
Production Capacity ◽  
Cell Marker ◽  
Natural Cytotoxicity ◽  
Lineage Markers

Abstract A subset of natural killer (NK) cells in normal mouse lymph node (LN) expresses CD127 (IL-7 receptor-α chain) and is thought to derive from the thymus. However, CD127+ NK cells are found in the LN of athymic mice. Therefore, the origin of CD127+ NK cells in the LN is unclear. Here, we have identified unique NK-cell progenitors (NKPs) in the LN that express the pan-NK cell marker CD49b and CD127 but lack CD122 and lineage markers. The LN NKPs develop in vitro into CD127+ NK cells that display natural cytotoxicity and cytokine production capacity. They also become CD127+ NK cells in lymphopenic mice that received a transplant. LN NKPs can be divided into stem cell antigen-1 (Sca-1)hi and Sca-1lo subsets. The latter comprise ∼ 60% of LN NKPs in normal mouse and < 10% of athymic mouse LN NKPs. Whereas both Sca-1hi and Sca-1lo NKPs develop into CD127+ NK cells in vitro, only those derived from Sca-1lo LN NKPs have rearranged TCRγ genes. Thus, CD127+ NK cells in the LN seem to be generated, at least in part, from both thymus-dependent Sca-1lo and thymus-independent Sca-1hi LN NKPs.

scholarly journals HLA-DR-Positive NK Cells Expand in Response to Mycobacterium Tuberculosis Antigens and Mediate Mycobacteria-Induced T Cell Activation

2021 ◽  
Vol 12 ◽  
Author(s):  
Sofya A. Kust ◽  
Maria A. Streltsova ◽  
Alexander V. Panteleev ◽  
Natalya L. Karpina ◽  
Irina V. Lyadova ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Nk Cells ◽  
Mhc Class Ii ◽  
T Cell Activation ◽  
Cell Activation ◽  
Nk Cell ◽  
Adaptive Immune Response ◽  
Hla Dr ◽  
High Responsiveness

NK cells play an important role in the control of tuberculosis infection: they are not only able to kill the infected cells, but also control the activity of macrophages and development of the adaptive immune response. Still, there is little information on the role of specific NK cell subsets in this network. In this study, we focused on the mycobacteria-driven responses of the NK cells expressing HLA-DR – a type of MHC class II. We have revealed that this subset is increased in the peripheral blood of patients with primary diagnosed tuberculosis, and expands in response to in vitro stimulation with ultrasonically destroyed Mycobacterium tuberculosis cells (sonicate). The expanded HLA-DR+ NK cells had less differentiated phenotype, higher proliferative activity and increased expression of NKp30 and NKp46 receptors. HLA-DR+CD56dim NK cells showed higher IFNγ production and degranulation level than the respective HLA-DR− NK cells in response to both 24 h and 7 day stimulation with sonicate, while HLA-DR+CD56bright NK cells mostly demonstarted similar high responsiveness to the same stimulating conditions as their HLA-DR−CD56bright counterparts. After preliminary incubation with destroyed mycobacteria, cytokine-activated HLA-DR-expressing NK cells were able to mediate mycobacteria-induced and HLA-DR-dependent cytokine production in autologous CD4+ T cells. Thus, functionally active HLA-DR+ cells seem to be one of the NK cell subsets providing an important link to the adaptive immunity.

scholarly journals HMGB1 translocation and release mediate cigarette smoke–induced pulmonary inflammation in mice through a TLR4/MyD88-dependent signaling pathway

2017 ◽  
Vol 28 (1) ◽  
pp. 201-209 ◽  
Author(s):  
Yao Cheng ◽  
Dan Wang ◽  
Bin Wang ◽  
Huanan Li ◽  
Junjie Xiong ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Signaling Pathway ◽  
Cigarette Smoke ◽  
Proinflammatory Cytokine ◽  
Cytokine Production ◽  
Pulmonary Inflammation ◽  
High Mobility ◽  
Lung Epithelial Cells ◽  
Proinflammatory Cytokine Production ◽  
Tnf Α

We performed studies to determine the role of high-mobility group box 1 (HMGB1) in cigarette smoke (CS)–induced pulmonary inflammation. After mice were exposed to five cigarettes four times a day for 3 d, toll-like receptor 4 (TLR4) expression and TLR4-mediated signaling were significantly up-regulated, and HMGB1 had translocated from the nucleus to the cytoplasm in lung epithelial cells and then been released into the extracellular lung space. On CS exposure, inflammatory cell recruitment and proinflammatory cytokine production were significantly increased in lung tissue and bronchoalveolar lavage, and these effects depended on the TLR4 signaling pathway. HMGB1 inhibition decreased the CS-induced inflammatory response, whereas treatment with exogenous HMGB1 aggravated the damage and increased the phosphorylation of JNK, p38, and IκBα in the lungs of wild-type mice but not in TLR4-knockout mice. Blockade of TLR4 action or TLR4 knockout significantly inhibited HMGB1-induced proinflammatory cytokine production in mouse tracheal epithelial (MTE) cells and lung tissues. In addition, a MyD88 deficiency inhibited JNK, p38, and IκBα phosphorylation, and this effect was associated with the suppressed production of TNF-α and IL-1β in MTE cells and lung tissues in response to CS stimulation. Thus HMGB1 activates the NF-κB and JNK/p38 pathways through TLR4/MyD88-dependent signaling and induces an inflammatory response in lungs exposed to CS.

Ketamine Suppresses Proinflammatory Cytokine Production in Human Whole Blood In Vitro

1999 ◽  
Vol 89 (3) ◽  
pp. 665 ◽  
Author(s):  
Takashi Kawasaki ◽  
Masanori Ogata ◽  
Chika Kawasaki ◽  
Jun-ichi Ogata ◽  
Yoshitaka Inoue ◽  
...  
Keyword(s):  
Whole Blood ◽  
Proinflammatory Cytokine ◽  
Cytokine Production ◽  
Proinflammatory Cytokine Production ◽  
Human Whole Blood

Consistency matters: Consistency in the timing and quality of daily interactions between parents and adolescents predicts production of proinflammatory cytokines in youths

2017 ◽  
Vol 30 (2) ◽  
pp. 373-382 ◽  
Author(s):  
Erika M. Manczak ◽  
Adam K. K. Leigh ◽  
Chia-Ping Chin ◽  
Edith Chen
Keyword(s):  
Relationship Quality ◽  
Proinflammatory Cytokines ◽  
Proinflammatory Cytokine ◽  
Cytokine Production ◽  
Leisure Activities ◽  
Proinflammatory Cytokine Production ◽  
Parent Child Relationship ◽  
Parent Child

AbstractThe current study examined whether consistency in day-to-day interactions between children and parents related to inflammatory cytokine production in youths. One hundred twenty-three parents recorded the daily quality of interactions and timing of leisure activities with their adolescent children for 2 weeks, and the degree of variability in those ratings was calculated. One year later, the production of proinflammatory cytokines in youths’ blood was measured in response to in vitro exposure to lipopolysaccharide (a bacterial product). The results indicate that greater variability in parent–child relationship quality related to greater stimulated proinflammatory cytokine production in youths, above and beyond overall relationship quality. Greater variability in the timing of parent–child leisure activities also predicted greater stimulated proinflammatory cytokine production in youths, regardless of the frequency of interactions. In sum, consistency in both the affective and temporal aspects of parent–child relationships may contribute to inflammatory processes in youth.

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