Monocyte-lymphocyte cross-communication via soluble CD163 directly links innate immune system activation and adaptive immune system suppression following ischemic stroke

AbstractCD163 is a scavenger receptor expressed on innate immune cell populations which can be shed from the plasma membrane via the metalloprotease ADAM17 to generate a soluble peptide with lympho-inhibitory properties. The purpose of this study was to investigate CD163 as a possible effector of stroke-induced adaptive immune system suppression. Liquid biopsies were collected from ischemic stroke patients (n=39), neurologically asymptomatic controls (n=20), and stroke mimics (n=20) within 24 hours of symptom onset. Peripheral blood ADAM17 activity and soluble CD163 levels were elevated in stroke patients relative to non-stroke control groups, and negatively associated with post-stroke lymphocyte counts. Subsequent in vitro experiments suggested that this stroke-induced elevation in circulating soluble CD163 likely originates from activated monocytic cells, as serum from stroke patients stimulated ADAM17-dependant CD163 shedding from healthy donor-derived monocytes. Additional in vitro experiments demonstrated that stroke-induced elevations in circulating soluble CD163 can elicit direct suppressive effects on the adaptive immune system, as serum from stroke patients inhibited the proliferation of healthy donor-derived lymphocytes, an effect which was attenuated following serum CD163 depletion. Collectively, these observations provide novel evidence that the innate immune system employs protective mechanisms aimed at mitigating the risk of post-stroke autoimmune complications driven by adaptive immune system overactivation, and that CD163 is key mediator of this phenomenon.

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The Complexity of the Innate Immune System Activation in Stroke Pathogenesis

Neuroinflammation ◽

10.1002/9781118732748.ch5 ◽

2015 ◽

pp. 71-85

Author(s):

María Isabel Cuartero ◽

Ignacio Lizasoain ◽

María Ángeles Moro ◽

Ivan Ballesteros

Keyword(s):

Immune System ◽

Innate Immune System ◽

Innate Immune ◽

Immune System Activation ◽

System Activation

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F.41. Innate Immune System Activation by Zymosan is Impaired by the R753Q Mutation in Toll-Like-Receptor (TLR)-2

Clinical Immunology ◽

10.1016/j.clim.2009.03.306 ◽

2009 ◽

Vol 131 ◽

pp. S105

Author(s):

Rima Abdel Massih ◽

Seung Kang ◽

Robert Brown ◽

Raymund Razonable

Keyword(s):

Immune System ◽

Innate Immune System ◽

Innate Immune ◽

Toll Like Receptor ◽

Immune System Activation ◽

System Activation

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Antibody equivalent molecules of the innate immune system: parallels between innate and adaptive immune proteins

Innate Immunity ◽

10.1177/1753425910370498 ◽

2010 ◽

Vol 16 (3) ◽

pp. 131-137 ◽

Cited By ~ 19

Author(s):

Nades Palaniyar

Keyword(s):

Pattern Recognition ◽

Immune System ◽

Innate Immune System ◽

Adaptive Immune System ◽

Surfactant Protein ◽

Innate Immune ◽

Future Research ◽

Surfactant Protein D ◽

Adaptive Immune ◽

Carbohydrate Arrays

Soluble pattern-recognition innate immune proteins functionally resemble the antibodies of the adaptive immune system. Two major families of such proteins are ficolins and collectins or collagenous lectins (e.g. mannose-binding lectin [MBL], surfactant proteins [SP-A and SP-D] and conglutinin). In general, subunits of ficolins and collectins recognize the carbohydrate arrays of their targets via globular trimeric carbohydrate-recognition domains (CRDs) whereas IgG, IgM and other antibody isotypes recognize proteins via dimeric antigen-binding domains (Fab). Considering the structure and functions of these proteins, ficolins and MBL are analogous to molecules with the complement activating functions of C1q and the target recognition ability of IgG. Although the structure of SP-A is similar to MBL, it does not activate the complement system. Surfactant protein-D and conglutinin could be considered as the collagenous non-complement activating giant IgMs of the innate immune system. Proteins such as peptidoglycan-recognition proteins, pentraxins and agglutinin gp-340/DMBT1 are also pattern-recognition proteins. These proteins may be considered as different isotypes of antibody-like molecules. Proteins such as defensins, cathelicidins and lactoferrins directly or indirectly alter microbes or microbial growth. These proteins may not be considered as antibodies of the innate immune system. Hence, ficolins and collectins could be considered as specialized ‘antibodies of the innate immune system’ instead of ‘ante-antibody’ innate immune molecules. The discovery, structure, functions and future research directions of many of these soluble proteins and receptors such as Toll-like and NOD-like receptors are discussed in this special issue of Innate Immunity.

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Impact of Microorganisms and Parasites on Neuronally Controlled Drosophila Behaviours

Cells ◽

10.3390/cells10092350 ◽

2021 ◽

Vol 10 (9) ◽

pp. 2350

Author(s):

Martina Montanari ◽

Julien Royet

Keyword(s):

Immune System ◽

Animal Behavior ◽

Innate Immune System ◽

Adaptive Immune System ◽

Model System ◽

Innate Immune ◽

Pathogenic Microorganisms ◽

Immune Systems ◽

Adaptive Immune ◽

Drosophila Model

Like all invertebrates, flies such as Drosophila lack an adaptive immune system and depend on their innate immune system to protect them against pathogenic microorganisms and parasites. In recent years, it appears that the nervous systems of eucaryotes not only control animal behavior but also cooperate and synergize very strongly with the animals’ immune systems to detect and fight potential pathogenic threats, and allow them to adapt their behavior to the presence of microorganisms and parasites that coexist with them. This review puts into perspective the latest progress made using the Drosophila model system, in this field of research, which remains in its infancy.

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Basic Immunology

Tutorial Topics in Infection for the Combined Infection Training Programme ◽

10.1093/oso/9780198801740.003.0012 ◽

2019 ◽

Author(s):

Jonathan Lambourne ◽

Ruaridh Buchanan

Keyword(s):

Immune Response ◽

Immune System ◽

Epithelial Cells ◽

Immune Cells ◽

Innate Immune System ◽

Adaptive Immune System ◽

Lymphoid Organs ◽

Innate Immune ◽

Adaptive Immune ◽

Pathogen Entry

There are four major components of the immune system. These include: 1. mechanical barriers to pathogen entry. 2. the innate immune system. 3. the adaptive immune system. 4. the lymphoid organs. Mechanical barriers include skin and mucous membranes and tight junctions between epithelial cells prevent pathogen entry. Breaches can be iatrogenic, for example, IV lines, surgical wounds, and mucositis, and are a large source of healthcare- associated infections. The innate immune system provides the first internal line of defence, as well as initiating and shaping the adaptive immune response. The innate system comprises a range of responses: phagocytosis by neutrophils and macrophages (guided in part by the adaptive immune system), the complement cascade, and the release of antimicrobial peptides by epithelial cells (e.g. defensins, cathelicidin). The adaptive immune system includes both humoral (antibody- mediated) and cell-mediated responses. It is capable of greater diversity and specificity than the innate immune system, and can develop memory to pathogens and provide increased protection on re-exposure. Immune cells are divided into myeloid cells (neutrophils, eosinophils, basophils, mast cells, and monocytes/macrophages) and lymphoid cells (B, T, and NK cells). These all originate in the bone marrow from pluripotent haematopoietic stem cells. The lymphoid organs include the spleen, the lymph nodes, and mucosal-associated lymphoid tissues—which respond to antigens in the blood, tissues, and epithelial surfaces respectively. The three main ‘professional’ phagocytes are macrophages, dendritic cells, and neutrophils. They are similar with respect to how they recognize pathogens, but differ in their principal location and effector functions. Phagocytes express an array of Pattern Recognition Receptors (PRRs) e.g. Toll-like receptors and lectins (proteins that bind carbohydrates). PRRs recognize Pathogen- Associated Molecular Patterns (PAMPs)— elements which are conserved across species, such as cell-surface glycoproteins and nucleic acid sequences. Though limited in number, PRRs have evolved to recognize a huge array of pathogens. Binding of PRRs to PAMPs enhances phagocytosis. Macrophages are tissue-resident phagocytes, initiating and co-ordinating the local immune response. The cytokines and chemokines they produce cause vasodilation and alter the expression of endothelial cell adhesion factors, recruiting circulating immune cells.

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Are autoimmune diseases autoinflammatory: Is it time to change the paradigm?

Lupus ◽

10.1177/09612033211038931 ◽

2021 ◽

pp. 096120332110389

Author(s):

Daniel Albert

Keyword(s):

Immune System ◽

Autoimmune Diseases ◽

Innate Immune System ◽

Adaptive Immune System ◽

Innate Immune ◽

Research Focus ◽

Adaptive Immune

The paradigm that autoimmune diseases are abberations in the adaptive immune system is over 50 years old, but recent data suggest a multitude of abnormalities in the innate immune system in lupus and other autoimmune diseases. This viewpoint elaborates the reasons that I think it is time to reexamine this paradigm and shift our research focus to the innate immune system in lupus and other prototypic autoimmune diseases.

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Innate immune system activation by viral RNA: How to predict it?

Virology ◽

10.1016/j.virol.2015.11.007 ◽

2016 ◽

Vol 488 ◽

pp. 169-178 ◽

Cited By ~ 5

Author(s):

M. Kondili ◽

M. Roux ◽

N. Vabret ◽

M. Bailly-Bechet

Keyword(s):

Immune System ◽

Innate Immune System ◽

Innate Immune ◽

Viral Rna ◽

Immune System Activation ◽

System Activation

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Toll-like receptors and damage-associated molecular patterns: novel links between inflammation and hypertension

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00328.2013 ◽

2014 ◽

Vol 306 (2) ◽

pp. H184-H196 ◽

Cited By ~ 105

Author(s):

Cameron G. McCarthy ◽

Styliani Goulopoulou ◽

Camilla F. Wenceslau ◽

Kathryn Spitler ◽

Takayuki Matsumoto ◽

...

Keyword(s):

Immune System ◽

Innate Immune System ◽

Cell Injury ◽

Receptor Activation ◽

Innate Immune ◽

Immune System Activation ◽

System Activation ◽

Molecular Patterns ◽

Damage Associated Molecular Patterns

Low-grade systemic inflammation is a common manifestation of hypertension; however, the exact mechanisms that initiate this pathophysiological response, thereby contributing to further increases in blood pressure, are not well understood. Aberrant vascular inflammation and reactivity via activation of the innate immune system may be the first step in the pathogenesis of hypertension. One of the functions of the innate immune system is to recognize and respond to danger. Danger signals can arise from not only pathogenic stimuli but also endogenous molecules released following cell injury and/or death [damage-associated molecular patterns (DAMPs)]. In the short-term, activation of the innate immune system is beneficial in the vasculature by providing cytoprotective mechanisms and facilitating tissue repair following injury or infection. However, sustained or excessive immune system activation, such as in autoimmune diseases, may be deleterious and can lead to maladaptive, irreversible changes to vascular structure and function. An initial source of DAMPs that enter the circulation to activate the innate immune system could arise from modest elevations in peripheral vascular resistance. These stimuli could subsequently lead to ischemic- or pressure-induced events aggravating further cell injury and/or death, providing more DAMPs for innate immune system activation. This review will address and critically evaluate the current literature on the role of the innate immune system in hypertension pathogenesis. The role of Toll-like receptor activation on somatic cells of the vasculature in response to the release of DAMPs and the consequences of this activation on inflammation, vasoreactivity, and vascular remodeling will be specifically discussed.

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