Regulation of the innate immune system by autophagy: neutrophils, eosinophils, mast cells, NK cells

Natural killer (NK) cells are innate lymphoid cells that recognize and eliminate virally-infected and cancerous cells. Members of the innate immune system are not usually considered to mediate immune memory, but over the past decade evidence has emerged that NK cells can do this in several contexts. Of these, the best understood and most widely accepted is the response to cytomegaloviruses, with strong evidence for memory to murine cytomegalovirus (MCMV) and several lines of evidence suggesting that the same is likely to be true of human cytomegalovirus (HCMV). The importance of NK cells in the context of HCMV infection is underscored by the armory of NK immune evasion genes encoded by HCMV aimed at subverting the NK cell immune response. As such, ongoing studies that have utilized HCMV to investigate NK cell diversity and function have proven instructive. Here, we discuss our current understanding of NK cell memory to viral infection with a focus on the response to cytomegaloviruses. We will then discuss the implications that this will have for the development of a vaccine against HCMV with particular emphasis on how a strategy that can harness the innate immune system and NK cells could be crucial for the development of a vaccine against this high-priority pathogen.

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

Cancers ◽

10.3390/cancers12082226 ◽

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.

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Inflammation of the cystic fibrosis mouse small intestine

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00473.2003 ◽

2004 ◽

Vol 286 (6) ◽

pp. G1032-G1041 ◽

Cited By ~ 97

Author(s):

Oxana Norkina ◽

Simran Kaur ◽

Donna Ziemer ◽

Robert C. De Lisle

Keyword(s):

Gene Expression ◽

Cystic Fibrosis ◽

Small Intestine ◽

Immune System ◽

Mast Cells ◽

Innate Immune System ◽

Innate Immune ◽

Serum Amyloid ◽

Mouse Small Intestine ◽

Cytochrome P 450

The CFTR null mouse [cystic fibrosis (CF) mouse] has a severe intestinal phenotype that serves as a model for CF-related growth deficiency, meconium ileus, and distal intestinal obstructive syndrome. DNA microarray analysis was used to investigate gene expression in the CF mouse small intestine. Sixty-one genes exhibited a statistically significant twofold or greater increase in expression, and 98 genes were downregulated twofold or greater. Of the upregulated genes, most were associated with inflammation and included markers for cells of the innate immune system (mast cells and neutrophils) and for acute-phase genes (serum amyloid A and complement factors). The downregulated genes include 10 cytochrome P-450 genes; several are involved in lipid metabolism, and several are involved in various transport processes. Confirmation by quantitative RT-PCR showed gene expression was significantly increased for mast cell protease 2 (27-fold), hematopoietic cell transcript 1 (17-fold), serum amyloid A3 (2.9-fold), suppressor of cytokine signaling 3 (2.0-fold), leucine-rich α2-glycoprotein (21-fold), resistin-like molecule-β (49-fold), and Muclin (2.5-fold) and was significantly decreased for cytochrome P-450 4a10 (28-fold) and cubilin (114-fold). Immune cell infiltration was confirmed histologically by staining for mast cells and neutrophils. These data demonstrate that the CF intestine exhibits an inflammatory state with upregulation of components of the innate immune system.

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Potent Stimulation of the Innate Immune System by aLeishmania brasiliensis Recombinant Protein

Infection and Immunity ◽

10.1128/iai.69.9.5270-5277.2001 ◽

2001 ◽

Vol 69 (9) ◽

pp. 5270-5277 ◽

Cited By ~ 30

Author(s):

Monamaris M. Borges ◽

Antonio Campos-Neto ◽

Paul Sleath ◽

Keneth H. Grabstein ◽

Philip J. Morrissey ◽

...

Keyword(s):

Pattern Recognition ◽

Immune System ◽

Nk Cells ◽

Innate Immune System ◽

Reticuloendothelial System ◽

Scid Mice ◽

Innate Immune ◽

Initiation Factor ◽

Interleukin 12 ◽

Microbial World

ABSTRACT The interaction of the innate immune system with the microbial world involves primarily two sets of molecules generally known as microbial pattern recognition receptors and microbial pattern recognition molecules, respectively. Examples of the former are the Toll receptors present particularly in macrophages and dendritic cells. Conversely, the microbial pattern recognition molecules are conserved protist homopolymers, such as bacterial lipopolysaccharides, lipoteichoic acids, peptidoglycans, glucans, mannans, unmethylated bacterial DNA, and double-strand viral RNA. However, for protists that lack most of these molecules, such as protozoans, the innate immune system must have evolved receptors that recognize other groups of microbial molecules. Here we present evidence that a highly purified protein encoded by a Leishmania brasiliensis gene may be one such molecule. This recombinant leishmanial molecule, a homologue of eukaryotic ribosomal elongation and initiation factor 4a (LeIF), strongly stimulates spleen cells from severe combined immunodeficient (SCID) mice to produce interleukin-12 (IL-12), IL-18, and high levels of gamma interferon. In addition, LeIF potentiates the cytotoxic activity of the NK cells of these animals. Because LeIF is a conserved molecule and because SCID mice lack T and B lymphocytes but have a normal innate immune system (normal reticuloendothelial system and NK cells), these results suggest that proteins may also be included as microbial pattern recognition molecules. The nature of the receptor involved in this innate recognition is unknown. However, it is possible to exclude the Toll receptor Tlr4 as a putative LeIF receptor because the gene encoding this receptor is defective in C3H/HeJ mice, the mouse strain used in the present studies.

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Pre- and Postictal Changes in the Innate Immune System: Cause or Effect?

European Neurology ◽

10.1159/000516556 ◽

2021 ◽

pp. 1-9

Author(s):

Johannes D. Lang ◽

David G. Olmes ◽

Manuel Proske ◽

Mareike Hagge ◽

Müjgan Dogan Onugoren ◽

...

Keyword(s):

Immune System ◽

Nk Cells ◽

Innate Immune System ◽

Mononuclear Cells ◽

Sampling Period ◽

Innate Immune ◽

Peripheral Blood Mononuclear ◽

Cytokine Analysis ◽

Inflammatory Processes ◽

Active Epilepsy

Introduction: Recent studies have shown that inflammatory processes might play a role in epileptogenesis. Their role in ictogenesis is much less clear. The aim of this study was to investigate peri-ictal changes of the innate immune system by analyzing changes of immune cells, as well as pro- and anti-inflammatory cytokines. Methods: Patients with active epilepsy admitted for video-EEG monitoring for presurgical evaluation were included. Blood was sampled every 20 min for 5 h on 3 consecutive days until a seizure occurred. After a seizure, additional samples were drawn immediately, as well as 1 and 24 h later. To analyze the different populations of peripheral blood mononuclear cells, all samples underwent FACS for CD3, CD4, CD8, CD56, CD14, CD16, and CD19. For cytokine analysis, we used a custom bead-based multiplex immunoassay for IFN-γ, IL-1β, IL-1RA, IL-4, IL-6, IL-10, IL-12, IL-17, MCP-1, MIP-1α, and TNFα. Results: Fourteen patients with focal seizures during the sampling period were included. Natural killer (NK) cells showed a negative correlation (ρ = −0.3362, p = 0.0195) before seizure onset and an immediate increase to 1.95-fold afterward. T helper (TH) and B cells decreased by 2 and 8%, respectively, in the immediate postictal interval. Nonclassical and intermediate monocytes decreased not until 1 day after the seizures, and cytotoxic T (TC) cells showed a long-lasting postictal increase by 4%. IL-10 and MCP-1 increased significantly after seizures, and IL-12 decreased in the postictal phase. Discussion/Conclusion: Our study argues for a role of the innate immune system in the pre- and postictal phases. NK cells might be involved in preictal changes or be altered as an epiphenomenon in the immediate preictal interval.

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The Memories of NK Cells: Innate-Adaptive Immune Intrinsic Crosstalk

Journal of Immunology Research ◽

10.1155/2016/1376595 ◽

2016 ◽

Vol 2016 ◽

pp. 1-14 ◽

Cited By ~ 14

Author(s):

Sara Gabrielli ◽

Claudio Ortolani ◽

Genny del Zotto ◽

Francesca Luchetti ◽

Barbara Canonico ◽

...

Keyword(s):

Immune System ◽

Nk Cells ◽

Innate Immune System ◽

Adaptive Immune System ◽

Point Of View ◽

Innate Immune ◽

Adaptive Immune ◽

System A ◽

Evolutionary Point

Although NK cells are considered part of the innate immune system, a series of evidences has demonstrated that they possess characteristics typical of the adaptive immune system. These NK adaptive features, in particular their memory-like functions, are discussed from an ontogenetic and evolutionary point of view.

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The role of Natural killer (NK) cells as APCs, Cytotoxicity, Immuno-regulatory in Innate and Adaptive immune as Potential Therapeutic and Preventive Target in Infectious Diseases

International Journal of Scientific and Engineering Research ◽

10.14299/ijser.2021.04.09 ◽

2021 ◽

Vol 12 (04) ◽

pp. 415-437

Author(s):

Dr. Zelalem Kiros Bitsue

Keyword(s):

Immune System ◽

Nk Cells ◽

Natural Killer ◽

Host Defense ◽

Immune Regulation ◽

Innate Immune System ◽

Adaptive Immune System ◽

Innate Immune ◽

Adaptive Immune

Natural killer (NK) cells are lymphocytes of the innate immune system that are critical in host defense and immune regulation. They are activated or inhibited through the ligation of germline-encoded receptors and are involved in mediating cytotoxicity, in producing cytokines and in providing co-stimulation to cells of the adaptive immune system.

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The Innate Immune System and Cardiovascular Disease in ESKD: Monocytes and Natural Killer Cells

Current Vascular Pharmacology ◽

10.2174/1570161118666200628024027 ◽

2020 ◽

Vol 19 (1) ◽

pp. 63-76 ◽

Cited By ~ 1

Author(s):

Evangelia Dounousi ◽

Anila Duni ◽

Katerina K. Naka ◽

Georgios Vartholomatos ◽

Carmine Zoccali

Keyword(s):

Heart Failure ◽

Cardiovascular Disease ◽

Immune System ◽

Kidney Disease ◽

Nk Cells ◽

Natural Killer ◽

Innate Immune System ◽

Nkt Cells ◽

Innate Immune ◽

Monocyte Subsets

Adverse innate immune responses have been implicated in several disease processes, including cardiovascular disease (CVD) and chronic kidney disease (CKD). The monocyte subsets natural killer (NK) cells and natural killer T (NKT) cells are involved in innate immunity. Monocytes subsets are key in atherogenesis and the inflammatory cascade occurring in heart failure. Upregulated activity and counts of proinflammatory CD16+ monocyte subsets are associated with clinical indices of atherosclerosis, heart failure syndromes and CKD. Advanced CKD is a complex state of persistent systemic inflammation characterized by elevated expression of proinflammatory and pro-atherogenic CD14++CD16+ monocytes, which are associated with cardiovascular events and death both in the general population and among patients with CKD. Diminished NK cells and NKT cells counts and aberrant activity are observed in both coronary artery disease and end-stage kidney disease. However, evidence of the roles of NK cells and NKT cells in atherogenesis in advanced CKD is circumstantial and remains to be clarified. This review describes the available evidence regarding the roles of specific immune cell subsets in the pathogenesis of CVD in patients with CKD. Future research is expected to further uncover the links between CKD associated innate immune system dysregulation and accelerated CVD and will ideally be translated into therapeutic targets.

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Mesenchymal Stromal Cells and Natural Killer Cells: A Complex Story of Love and Hate

Current Stem Cell Research & Therapy ◽

10.2174/1574888x13666180912125736 ◽

2019 ◽

Vol 14 (1) ◽

pp. 14-21 ◽

Cited By ~ 3

Author(s):

Mehdi Najar ◽

Mohammad Fayyad-Kazan ◽

Makram Merimi ◽

Arsène Burny ◽

Dominique Bron ◽

...

Keyword(s):

Immune System ◽

Nk Cells ◽

Natural Killer ◽

Mesenchymal Stromal Cells ◽

Immune Cells ◽

Stromal Cells ◽

Innate Immune System ◽

Innate Immune ◽

Complex Interactions ◽

Cell Based Therapy

Mesenchymal stromal cells (MSCs), characterized by both multidifferentiation potential and potent immunomodulatory capacity, represent a promising, safe and powerful cell based-therapy for repairing tissue damage and/or treating diseases associated with aberrant immune responses. Natural killer (NK) cells are granular lymphocytes of the innate immune system that function alone or in combination with other immune cells to combat both tumors and virally infected cells. After their infusion, MSCs are guided by host inflammatory elements and can interact with different immune cells, particularly those of the innate immune system. Although some breakthroughs have been achieved in understanding these interactions, much remains to be determined. In this review, we discuss the complex interactions between NK cells and MSCs, particularly the importance of improving the therapeutic value of MSCs.

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Mast Cell and Autoimmune Diseases

Mediators of Inflammation ◽

10.1155/2015/246126 ◽

2015 ◽

Vol 2015 ◽

pp. 1-8 ◽

Cited By ~ 29

Author(s):

Yunzhi Xu ◽

Guangjie Chen

Keyword(s):

Rheumatoid Arthritis ◽

Multiple Sclerosis ◽

Mast Cell ◽

Immune System ◽

Mast Cells ◽

Autoimmune Diseases ◽

Innate Immune System ◽

Innate Immune ◽

Current Stage

Mast cells are important in innate immune system. They have been appreciated as potent contributors to allergic reaction. However, increasing evidence implicates the important role of mast cells in autoimmune disease like rheumatoid arthritis and multiple sclerosis. Here we review the current stage of knowledge about mast cells in autoimmune diseases.

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