scholarly journals TLR agonists enhance responsiveness of inflammatory innate immune cells in HLA-B*57-positive HIV patients

2020 ◽  
Vol 99 (1) ◽  
pp. 147-158
Author(s):  
L. Dold ◽  
L. Zimmer ◽  
C. Schwarze-Zander ◽  
C. Boesecke ◽  
R. Mohr ◽  
...  
Keyword(s):  
Hiv Infection ◽  
Nk Cells ◽  
Immune Cells ◽  
Nk Cell ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Double Positive ◽  
Hiv Patients ◽  
Ifn Gamma ◽  
Tlr Agonists

Abstract HLA-B*57 affects the course of HIV infection. Under antiretroviral therapy, its effects cannot be explained by outstandingly efficient T cell responses alone but may also involve cells of innate immunity. Studying in vitro stimulation with Pam3CSK4, E. coli LPS-B5 and CpG-ODN-2216, we observed greater induction of IL-6/IL-1beta double-positive CD14+CD16++ monocytes as well as IFN-gamma-positive cytotoxic CD56highCD16neg NK cells in HLA-B*57- versus HLA-B*44-positive HIV patients, while TNF-alpha induction remained unchanged. Differences were not seen in the other monocyte and NK cell subsets or in HLA-matched healthy controls. Our findings show that, in virally suppressed HIV infection, HLA-B*57 is associated with enhanced responsiveness of inflammatory innate immune cells to TLR ligands, possibly contributing to increased vulnerability in sepsis. Key messages • HLA-B*57 is a host factor affecting clinical outcomes of HIV infection. • HLA-B*57 modifies inflammatory subsets of NK cells and monocytes in HIV infection. • In HLA-B*57-positive HIV patients TLR agonists induce enhanced IL-6/IL-1beta in monocytes. • NK cells from HLA-B*57 HIV patients release more IFN-gamma upon TLR costimulation. • HLA-B*57 is linked to enhanced inflammatory responsiveness to TLR ligands.

scholarly journals Lower blood lactate and higher circulating natural killer cells at admission predict spontaneous survival in non-acetaminophen induced acute Liver failure

2020 ◽  
Author(s):  
Tanvi Agrawal ◽  
Rakhi Maiwall ◽  
Rajan V ◽  
Meenu Bajpai ◽  
Rakesh Kumar Jagdish ◽  
...  
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Immune Cells ◽  
Nk Cell ◽  
Innate Immune ◽  
List Type ◽  
Innate Immune Cells ◽  
Cell Percentage ◽  
Immune Mediated ◽  
Lactate Levels

AbstractBackground and AimsMassive cellular necrosis in ALF is dominantly immune mediated and innate immune cells are major pathophysiological determinants in liver damage. Our aim was to investigate specific innate immune cells or damage associated molecular patterns (DAMPs) relating to the final outcome of patient.MethodsIn fifty ALF patients and in fifteen age-matched healthy controls (HC), DAMPs were measured in plasma using ELISA. Phenotypic analysis of neutrophils, monocytes, natural killer (NK) and NKT cells was done by flow-cytometry and correlated with clinical and biochemical parameters.ResultsALF patients (aged 27±9 yr, 56% males, 78% viral etiology) had MELD of 31.5±8, jaundice to hepatic encephalopathy (HE) of 4.6±3.2 days, HE grade III-IV, 82% with cerebral edema, 38% met KCH criteria, 56% had suspected sepsis. Percentage of intermediate monocytes (CD14+CD16+) was increased (p<0.01) and non-classical monocytes (CD14-CD16+) was decreased in ALF compared to HC. CD16+CD56+ NK cells in total lymphocytes was significantly lower in ALF patients compared to HC, but was higher in survivors {9.28% (0.5-20.3)} than non-survivors {5.1% (0.2-10.6)} (p<0.001). Higher percentage of circulating NK cells (>6.7%) at admission was a good predictor of survival. Non-survivors had higher levels of serum lactate (6.1 vs. 28, Odds ratio 2.23, CI 1.27-3.94) and granzymeB positive NK cells than survivors. Logistic regression model predicted the combination of lactate levels with NK cell percentage at admission for survival (AUROC of 0.94; sensitivity 95.8%, specificity of 78.5%).ConclusionCombination of NK cell frequency and lactate levels at admission can reliably predict survival of ALF patients.KEY POINTSALF is generally immune mediated and predominantly caused by viral infections or acetaminophen toxicity.Therapeutic options are limited in ALF, important to know key immune players for their survival.CD16+CD56+ NK cells were found to be higher in survivors than non survivors.Combination of lactate levels with NK cell percentage at the time of admission can reliably predict the survival of ALF patients.

scholarly journals Toll-Like Receptors in Natural Killer Cells and Their Application for Immunotherapy

2020 ◽  
Vol 2020 ◽  
pp. 1-9 ◽  
Author(s):  
Ji-Yoon Noh ◽  
Suk Ran Yoon ◽  
Tae-Don Kim ◽  
Inpyo Choi ◽  
Haiyoung Jung
Keyword(s):  
Immune Responses ◽  
Nk Cells ◽  
Immune Cells ◽  
Viral Infections ◽  
Nk Cell ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Innate Immune Responses ◽  
Toll Like Receptors ◽  
Microbial Infection

Innate immunity represents the first barrier for host defense against microbial infection. Toll-like receptors (TLRs) are the most well-defined PRRs with respect to PAMP recognition and induction of innate immune responses. They recognize pathogen-associated molecular patterns (PAMPs) and trigger innate immune responses by inducing inflammatory cytokines, chemokines, antigen-presenting molecules, and costimulatory molecules. TLRs are expressed either on the cell surface or within endosomes of innate immune cells. NK cells are one of the innate immune cells and also express TLRs to recognize or respond to PAMPs. TLRs in NK cells induce the innate immune responses against bacterial and viral infections via inducing NK cytotoxicity and cytokine production. In this review, we will discuss the expression and cellular function of TLRs in NK cells and also introduce some therapeutic applications of TLR agonists for NK cell-mediated immunotherapy.

scholarly journals Sialic Acids and Their Influence on Human NK Cell Function

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 263
Author(s):  
Philip Rosenstock ◽  
Thomas Kaufmann
Keyword(s):  
Nk Cells ◽  
Immune Cells ◽  
Cell Function ◽  
Nk Cell ◽  
Sialic Acids ◽  
Innate Immune ◽  
Target Cells ◽  
Carbon Backbone ◽  
Nk Cell Receptors ◽  
Cell Inhibition

Sialic acids are sugars with a nine-carbon backbone, present on the surface of all cells in humans, including immune cells and their target cells, with various functions. Natural Killer (NK) cells are cells of the innate immune system, capable of killing virus-infected and tumor cells. Sialic acids can influence the interaction of NK cells with potential targets in several ways. Different NK cell receptors can bind sialic acids, leading to NK cell inhibition or activation. Moreover, NK cells have sialic acids on their surface, which can regulate receptor abundance and activity. This review is focused on how sialic acids on NK cells and their target cells are involved in NK cell function.

HIV infection: focus on the innate immune cells

2016 ◽  
Vol 64 (5-6) ◽  
pp. 1118-1132 ◽  
Author(s):  
Milena S. Espíndola ◽  
Luana S. Soares ◽  
Leonardo J. Galvão-Lima ◽  
Fabiana A. Zambuzi ◽  
Maira C. Cacemiro ◽  
...  
Keyword(s):  
Hiv Infection ◽  
Immune Cells ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Infection Focus

scholarly journals Adaptive and Innate Immune Cells in Fetal Human Cytomegalovirus-Infected Brains

2020 ◽  
Vol 8 (2) ◽  
pp. 176 ◽  
Author(s):  
Yann Sellier ◽  
Florence Marliot ◽  
Bettina Bessières ◽  
Julien Stirnemann ◽  
Ferechte Encha-Razavi ◽  
...  
Keyword(s):  
T Cells ◽  
Nk Cells ◽  
Immune Cells ◽  
Plasma Cells ◽  
Ex Vivo ◽  
Fetal Brain ◽  
Brain Lesions ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Infected Cells

Background: The understanding of the pathogenesis of cytomegalovirus (CMV)-induced fetal brain lesions is limited. We aimed to quantify adaptive and innate immune cells and CMV-infected cells in fetal brains with various degrees of brain damage. Methods: In total, 26 archived embedded fetal brains were studied, of which 21 were CMV-infected and classified in severely affected (n = 13) and moderately affected (n = 8), and 5 were uninfected controls. The respective magnitude of infected cells, immune cells (CD8+, B cells, plasma cells, NK cells, and macrophages), and expression of immune checkpoint receptors (PD-1/PD-L1 and LAG-3) were measured by immunochemistry and quantified by quantitative imaging analysis. Results: Quantities of CD8+, plasma cells, NK cells, macrophages, and HCMV+ cells and expression of PD-1/PD-L1 and LAG-3 were significantly higher in severely affected than in moderately affected brains (all p values < 0.05). A strong link between higher number of stained cells for HCMV/CD8 and PD-1 and severity of brain lesions was found by component analysis. Conclusions: The higher expression of CD8, PD-1, and LAG-3 in severely affected brains could reflect immune exhaustion of cerebral T cells. These exhausted T cells could be ineffective in controlling viral multiplication itself, leading to more severe brain lesions. The study of the functionality of brain leucocytes ex vivo is needed to confirm this hypothesis.

The role of IL-17 producing NK cells and other innate immune cells in poly(I:C) triggered exacerbation of experimental asthma

2016 ◽  
Author(s):  
Lars Lunding ◽  
Christina Vock ◽  
Sina Webering ◽  
Jochen Behrends ◽  
Christoph Hölscher ◽  
...  
Keyword(s):  
Nk Cells ◽  
Immune Cells ◽  
Innate Immune ◽  
Poly I:C ◽  
Innate Immune Cells

scholarly journals Elucidating the Innate Immunological Effects of Mild Magnetic Hyperthermia on U87 Human Glioblastoma Cells: An in vitro Study

2021 ◽  
Author(s):  
Stefano Persano ◽  
Francesco Vicini ◽  
Alessandro Poggi ◽  
Jordi Leonardo Castrillo Fernandez ◽  
Giusy Maria Rita Rizzo ◽  
...  
Keyword(s):  
Immune Cells ◽  
Immune Cell ◽  
Nk Cell ◽  
Magnetic Hyperthermia ◽  
Innate Immune ◽  
Target Cells ◽  
Innate Immune Cells ◽  
Glioblastoma Cells ◽  
Mild Hyperthermia ◽  
Wide Range

Cancer immunotherapies are gaining a large popularity and many of them have been approved as standard second-line or in some cases even as first-line treatment for a wide range of cancers. However, immunotherapy has not shown a clinically relevant success in glioblastoma (GBM), principally due to the brain&rsquo;s &ldquo;immune-privileged&rdquo; status and the peculiar tumor microenvironment (TME) of GBM featured by lack of presence of tumor-infiltrating lymphocytes and the establishment of immunosuppressive mechanisms. Emerging evidence has highlighted the key role played by innate immune cells in immunosurveillance and in initiating and driving immune responses against GBM. Immunogenic cell death (ICD) is a promising approach to elicit direct activation of the innate immune system by inducing in target cancer cells the expression of molecular signatures recognized through a repertoire of innate immune cell pattern recognition receptors (PRRs) by effector innate immune cells. Herein, we explored local mild thermal treatment, generated by using ultrasmall (size ~ 17 nm) cubic-shaped iron oxide nanoparticles exposed to an external alternating magnetic field (AMF), to induce ICD in U87 glioblastoma cells. In accordance with what has been previously observed with other types of tumors, we found that mild hyperthermia modulates the immunological profile of U87 glioblastoma cells by inducing stress-associated signals leading to enhanced phagocytosis and killing of U87 cells by macrophages. Finally, we demonstrated that mild magnetic hyperthermia has a modulatory effect on the expression of inhibitory and activating NK cell ligands on target cells. Interestingly, alteration in the expression of NK ligands, caused by mild hyperthermia treatment, in U87 glioblastoma cells, increased their susceptibility to NK cell killing and NK cell functionality. The overall findings demonstrate that mild magnetic hyperthermia stimulates ICD and sensitizes GBM cells to NK-mediated killing by inducing the upregulation of specific stress ligands, providing a novel immunotherapeutic approach for GBM treatment, with potential to synergize with existing NK cell-based therapies thus improving their therapeutic outcomes.

scholarly journals Chronic HIV infection induces transcriptional and functional reprogramming of innate immune cells

JCI Insight ◽  
2021 ◽  
Author(s):  
Wouter A. van der Heijden ◽  
Lisa van de Wijer ◽  
Farid Keramati ◽  
Wim Trypsteen ◽  
Sofie Rutsaert ◽  
...  
Keyword(s):  
Hiv Infection ◽  
Immune Cells ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Chronic Hiv Infection

scholarly journals Understanding the Role of Innate Immune Cells and Identifying Genes in Breast Cancer Microenvironment

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2226
Author(s):  
Israa Shihab ◽  
Bariaa A. Khalil ◽  
Noha Mousaad Elemam ◽  
Ibrahim Y. Hachim ◽  
Mahmood Yaseen Hachim ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune System ◽  
Tumor Microenvironment ◽  
Nk Cells ◽  
Immune Cells ◽  
Innate Immune System ◽  
Adaptive Immune System ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Cancer Microenvironment

The innate immune system is the first line of defense against invading pathogens and has a major role in clearing transformed cells, besides its essential role in activating the adaptive immune system. Macrophages, dendritic cells, NK cells, and granulocytes are part of the innate immune system that accumulate in the tumor microenvironment such as breast cancer. These cells induce inflammation in situ by secreting cytokines and chemokines that promote tumor growth and progression, in addition to orchestrating the activities of other immune cells. In breast cancer microenvironment, innate immune cells are skewed towards immunosuppression that may lead to tumor evasion. However, the mechanisms by which immune cells could interact with breast cancer cells are complex and not fully understood. Therefore, the importance of the mammary tumor microenvironment in the development, growth, and progression of cancer is widely recognized. With the advances of using bioinformatics and analyzing data from gene banks, several genes involved in NK cells of breast cancer individuals have been identified. In this review, we discuss the activities of certain genes involved in the cross-talk among NK cells and breast cancer. Consequently, altering tumor immune microenvironment can make breast tumors more responsive to immunotherapy.

HIV infection and aging of the innate immune system

Sexual Health ◽  
2011 ◽  
Vol 8 (4) ◽  
pp. 453 ◽  
Author(s):  
Anna C. Hearps ◽  
Thomas A. Angelovich ◽  
Anthony Jaworowski ◽  
John Mills ◽  
Alan L. Landay ◽  
...  
Keyword(s):  
Immune System ◽  
Hiv Infection ◽  
Immune Cells ◽  
Inflammatory Diseases ◽  
The Elderly ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Telomere Attrition ◽  
Age Related ◽  
The Impact

The increased life expectancy of HIV-infected individuals due to improved treatment has revealed an unexpected increase in non-AIDS comorbidities that are typically associated with older age including cardiovascular disease, dementia and frailty. The majority of these diseases arise as the result of dysregulated systemic inflammation, and both the aged and HIV-infected individuals exhibit elevated basal levels of inflammation. In the elderly, increased inflammation and age-related diseases are associated with a state of impaired immunity called immunosenescence, which is thought to result from a lifetime of immune stimulation. It is now apparent that HIV induces premature immunosenescence within T-cells; however, the impact of HIV on aging of cells of the innate arm of the immune system is unknown. Innate immune cells play a central role in inflammation and are thus critical for the pathogenesis of inflammatory diseases. Limited evidence suggests HIV infection mimics age-related changes to innate immune cells; however, the extent of this effect and the mechanism underlying these changes remain to be defined. This review focuses on the impact of HIV infection on the function and aging of innate immune cells and discusses potential drivers of premature immunosenescence including chronic endotoxaemia, residual viraemia, telomere attrition and altered cellular signalling.

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