From Coxiella burnetii Infection to Pregnancy Complications: Key Role of the Immune Response of Placental Cells

The infection of pregnant animals and women by Coxiella burnetii, an intracellular bacterium, compromises both maternal health and foetal development. The placenta is targeted by C. burnetii, as demonstrated by bacteriological and histological evidence. It now appears that placental strains of C. burnetii are highly virulent compared to reference strains and that placental injury involves different types of placental cells. Trophoblasts, the major placental cells, are largely infected by C. burnetii and may represent a replicating niche for the bacteria. The placenta also contains numerous immune cells, including macrophages, dendritic cells, and mast cells. Placental macrophages are infected and activated by C. burnetii in an unusual way of M1 polarisation associated with bacterial elimination. Placental mast cells eliminate bacteria through a mechanism including the release of extracellular actin filaments and antimicrobial peptides. In contrast, C. burnetii impairs the maturation of decidual dendritic cells, favouring bacterial pathogenicity. Our aim is to review C. burnetii infections of human placentas, paying special attention to both the action and function of the different cell types, immune cells, and trophoblasts targeted by C. burnetii in relation to foetal injury.

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Neuroinflammation in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia and the Interest of Induced Pluripotent Stem Cells to Study Immune Cells Interactions With Neurons

Frontiers in Molecular Neuroscience ◽

10.3389/fnmol.2021.767041 ◽

2021 ◽

Vol 14 ◽

Author(s):

Elise Liu ◽

Léa Karpf ◽

Delphine Bohl

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Immune System ◽

Frontotemporal Dementia ◽

Immune Cells ◽

Immune Cell ◽

Current Knowledge ◽

Cell Types ◽

Induced Pluripotent ◽

Different Cell Types ◽

Lateral Sclerosis

Inflammation is a shared hallmark between amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). For long, studies were conducted on tissues of post-mortem patients and neuroinflammation was thought to be only bystander result of the disease with the immune system reacting to dying neurons. In the last two decades, thanks to improving technologies, the identification of causal genes and the development of new tools and models, the involvement of inflammation has emerged as a potential driver of the diseases and evolved as a new area of intense research. In this review, we present the current knowledge about neuroinflammation in ALS, ALS-FTD, and FTD patients and animal models and we discuss reasons of failures linked to therapeutic trials with immunomodulator drugs. Then we present the induced pluripotent stem cell (iPSC) technology and its interest as a new tool to have a better immunopathological comprehension of both diseases in a human context. The iPSC technology giving the unique opportunity to study cells across differentiation and maturation times, brings the hope to shed light on the different mechanisms linking neurodegeneration and activation of the immune system. Protocols available to differentiate iPSC into different immune cell types are presented. Finally, we discuss the interest in studying monocultures of iPS-derived immune cells, co-cultures with neurons and 3D cultures with different cell types, as more integrated cellular approaches. The hope is that the future work with human iPS-derived cells helps not only to identify disease-specific defects in the different cell types but also to decipher the synergistic effects between neurons and immune cells. These new cellular tools could help to find new therapeutic approaches for all patients with ALS, ALS-FTD, and FTD.

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The Differential Anti-HIV Effect of a New Humic Substance-Derived Preparation in Diverse Cells of the Immune System

Acta Naturae ◽

10.32607/20758251-2019-11-2-68-76 ◽

2019 ◽

Vol 11 (2) ◽

pp. 68-76

Author(s):

G. V. Kornilaeva ◽

A. E. Siniavin ◽

A. Schultz ◽

A. Germann ◽

C. Moog ◽

...

Keyword(s):

Dendritic Cells ◽

T Lymphocytes ◽

Humic Substance ◽

Immune Cells ◽

Cell Types ◽

Inhibitory Effect ◽

Infection Inhibition ◽

Toxic Concentrations ◽

Anti Hiv ◽

Hiv 1

The anti-HIV activity of a new humic substance-derived preparation has been studied in individual pools of immune cells (CD4+ T lymphocytes, macrophages, dendritic cells). Near-complete inhibition of the HIV infection (by more than 90%) was achieved by treating each of the abovementioned cell types with non-toxic concentrations of the preparation. The inhibitory effect demonstrates the possibility of preventing the depletion of a significant portion of functionally important immune cells. A comparative study of infection inhibition in individual cell pools has allowed us to reveal the differences in the preparations effectiveness in each of the cell populations. A R5-tropic HIV-1 infection in macrophages exhibited maximum sensitivity to the preparation: 90% and 50% inhibition of the infection were observed in the presence of concentrations as low as 1.4 and 0.35 g/ml, respectively. A 15- and 19-fold higher concentration was required to achieve the same extent of inhibition in dendritic cells infected with the same strain. The effectiveness of the drug in CD4 + T lymphocytes is quite comparable to its effectiveness in macrophages. The drug is universally effective for both the T- and M-tropic variants of HIV-1.

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Single cell analysis reveals immune cell–adipocyte crosstalk regulating the transcription of thermogenic adipocytes

eLife ◽

10.7554/elife.49501 ◽

2019 ◽

Vol 8 ◽

Cited By ~ 17

Author(s):

Prashant Rajbhandari ◽

Douglas Arneson ◽

Sydney K Hart ◽

In Sook Ahn ◽

Graciel Diamante ◽

...

Keyword(s):

Single Cell ◽

Immune Cells ◽

Immune Cell ◽

Single Cell Analysis ◽

Metabolic Response ◽

Cell Types ◽

Specific Cell ◽

Beneficial Effects ◽

Thermogenic Adipocytes ◽

And Function

Immune cells are vital constituents of the adipose microenvironment that influence both local and systemic lipid metabolism. Mice lacking IL10 have enhanced thermogenesis, but the roles of specific cell types in the metabolic response to IL10 remain to be defined. We demonstrate here that selective loss of IL10 receptor α in adipocytes recapitulates the beneficial effects of global IL10 deletion, and that local crosstalk between IL10-producing immune cells and adipocytes is a determinant of thermogenesis and systemic energy balance. Single Nuclei Adipocyte RNA-sequencing (SNAP-seq) of subcutaneous adipose tissue defined a metabolically-active mature adipocyte subtype characterized by robust expression of genes involved in thermogenesis whose transcriptome was selectively responsive to IL10Rα deletion. Furthermore, single-cell transcriptomic analysis of adipose stromal populations identified lymphocytes as a key source of IL10 production in response to thermogenic stimuli. These findings implicate adaptive immune cell-adipocyte communication in the maintenance of adipose subtype identity and function.

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Nonneuronal Cholinergic System in Breast Tumors and Dendritic Cells: Does It Improve or Worsen the Response to Tumor?

ISRN Cell Biology ◽

10.1155/2013/486545 ◽

2013 ◽

Vol 2013 ◽

pp. 1-12

Author(s):

Marisa Vulcano ◽

María Gabriela Lombardi ◽

María Elena Sales

Keyword(s):

Dendritic Cells ◽

Cholinergic System ◽

Parasympathetic Nervous System ◽

Immune Cell ◽

Breast Tumors ◽

Cell Types ◽

Cellular Functions ◽

And Migration ◽

And Function

Besides being the main neurotransmitter in the parasympathetic nervous system, acetylcholine (ACh) can act as a signaling molecule in nonneuronal tissues. For this reason, ACh and the enzymes that synthesize and degrade it (choline acetyltransferase and acetylcholinesterase) as well as muscarinic (mAChRs) and nicotinic receptors conform the non-neuronal cholinergic system (nNCS). It has been reported that nNCS regulates basal cellular functions including survival, proliferation, adhesion, and migration. Moreover, nNCS is broadly expressed in tumors and in different components of the immune system. In this review, we summarize the role of nNCS in tumors and in different immune cell types focusing on the expression and function of mAChRs in breast tumors and dendritic cells (DCs) and discussing the role of DCs in breast cancer.

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Atherosclerosis: cellular mechanisms

10.1093/med/9780198755777.003.0013 ◽

2017 ◽

Author(s):

Esther Lutgens ◽

Marie-Luce Bochaton-Piallat ◽

Christian Weber

Keyword(s):

Immune Cells ◽

Adaptive Immune System ◽

Cell Types ◽

Chronic Inflammatory Disease ◽

Branch Points ◽

Cellular Mechanisms ◽

Blood Flow Dynamics ◽

Arterial Intima ◽

Different Cell Types

Atherosclerosis is a lipid-driven, chronic inflammatory disease of the large and middle-sized arteries that affects every human being and slowly progresses with age. The disease is characterized by the presence of atherosclerotic plaques consisting of lipids, (immune) cells, and debris that form in the arterial intima. Plaques develop at predisposed regions characterized by disturbed blood flow dynamics, such as curvatures and branch points. In the past decades, experimental and patient studies have revealed the role of the different cell-types of the innate and adaptive immune system, and of non-immune cells such as platelets, endothelial, and vascular smooth muscle cells, in its pathogenesis. This chapter highlights the roles of these individual cell types in atherogenesis and explains their modes of communication using chemokines, cytokines, and co-stimulatory molecules.

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Engineering advanced logic and distributed computing in human CAR immune cells

Nature Communications ◽

10.1038/s41467-021-21078-7 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Jang Hwan Cho ◽

Atsushi Okuma ◽

Katri Sofjan ◽

Seunghee Lee ◽

James J. Collins ◽

...

Keyword(s):

Immune Cells ◽

Communication Channel ◽

Immune Cell ◽

Cell Types ◽

Innate Immune ◽

Innate Immune Cells ◽

Complex Phenotypes ◽

Car T ◽

Different Cell Types ◽

Multiple Immune Cell

AbstractThe immune system is a sophisticated network of different cell types performing complex biocomputation at single-cell and consortium levels. The ability to reprogram such an interconnected multicellular system holds enormous promise in treating various diseases, as exemplified by the use of chimeric antigen receptor (CAR) T cells as cancer therapy. However, most CAR designs lack computation features and cannot reprogram multiple immune cell types in a coordinated manner. Here, leveraging our split, universal, and programmable (SUPRA) CAR system, we develop an inhibitory feature, achieving a three-input logic, and demonstrate that this programmable system is functional in diverse adaptive and innate immune cells. We also create an inducible multi-cellular NIMPLY circuit, kill switch, and a synthetic intercellular communication channel. Our work highlights that a simple split CAR design can generate diverse and complex phenotypes and provide a foundation for engineering an immune cell consortium with user-defined functionalities.

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A systems perspective of heterocellular signaling

Essays in Biochemistry ◽

10.1042/ebc20180015 ◽

2018 ◽

Vol 62 (4) ◽

pp. 607-617 ◽

Cited By ~ 3

Author(s):

Alan Wells ◽

H. Steven Wiley

Keyword(s):

Cell Types ◽

Regulatory Processes ◽

Technical Developments ◽

Building Models ◽

Realistic Description ◽

Multiple Cell ◽

Solid Foundation ◽

And Function ◽

Multicellular Organisms ◽

Different Cell Types

Signal exchange between different cell types is essential for development and function of multicellular organisms, and its dysregulation is causal in many diseases. Unfortunately, most cell-signaling work has employed single cell types grown under conditions unrelated to their native context. Recent technical developments have started to provide the tools needed to follow signaling between multiple cell types, but gaps in the information they provide have limited their usefulness in building realistic models of heterocellular signaling. Currently, only targeted assays have the necessary sensitivity, selectivity, and spatial resolution to usefully probe heterocellular signaling processes, but these are best used to test specific, mechanistic models. Decades of systems biology research with monocultures has provided a solid foundation for building models of heterocellular signaling, but current models lack a realistic description of regulated proteolysis and the feedback processes triggered within and between cells. Identification and understanding of key regulatory processes in the extracellular environment and of recursive signaling patterns between cells will be essential to building predictive models of heterocellular systems.

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Crosstalk Between Tumor-Associated Microglia/Macrophages and CD8-Positive T Cells Plays a Key Role in Glioblastoma

Frontiers in Immunology ◽

10.3389/fimmu.2021.650105 ◽

2021 ◽

Vol 12 ◽

Author(s):

Sheng Tu ◽

Xu Lin ◽

Jili Qiu ◽

Jiaqi Zhou ◽

Hui Wang ◽

...

Keyword(s):

T Cells ◽

Cd8 T Cells ◽

Immune Cells ◽

Malignant Disease ◽

Immune Therapy ◽

Cell Types ◽

Different Types ◽

The Central Nervous System ◽

And Function ◽

The Relationship

Glioblastoma is considered to be the most malignant disease of the central nervous system, and it is often associated with poor survival. The immune microenvironment plays a key role in the development and treatment of glioblastoma. Among the different types of immune cells, tumor-associated microglia/macrophages (TAM/Ms) and CD8-positive (CD8+) T cells are the predominant immune cells, as well as the most active ones. Current studies have suggested that interaction between TAM/Ms and CD8+ T cells have numerous potential targets that will allow them to overcome malignancy in glioblastoma. In this review, we summarize the mechanism and function of TAM/Ms and CD8+ T cells involved in glioblastoma, as well as update on the relationship and crosstalk between these two cell types, to determine whether this association alters the immune status during glioblastoma development and affects optimal treatment. We focus on the molecular factors that are crucial to this interaction, and the role that this crosstalk plays in the biological processes underlying glioblastoma treatment, particularly with regard to immune therapy. We also discuss novel therapeutic targets that can aid in resolving reticular connections between TAM/Ms and CD8+ T cells, including depletion and reprogramming TAM/Ms and novel TAM/Ms-CD8+ T cell cofactors with potential translational usage. In addition, we highlight the challenges and discuss future perspectives of this crosstalk between TAM/Ms and CD8+ T cells.

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Neonatal Fc receptor (FcRn) – not only transporter of maternal IgG

Postępy Higieny i Medycyny Doświadczalnej ◽

10.5604/01.3001.0012.2094 ◽

2018 ◽

Vol 72 ◽

pp. 701-727

Author(s):

Joanna E. Mikulska

Keyword(s):

Mhc Class I ◽

Current Knowledge ◽

Cell Types ◽

Fc Receptor ◽

Class I ◽

Neonatal Fc Receptor ◽

The Status ◽

And Function ◽

Different Cell Types ◽

Maternal Igg

The neonatal Fc receptor, (FcRn) is a transmembrane, heterodimeric glycoprotein with a structure similar to MHC class I molecules. In contrast to MHC class I antigens, FcRn does not bind to peptides (antigens) but interacts with the Fc fragment of IgG and albumin. The FcRn-IgG interaction as well as the FcRn-albumin interaction occur at acidic pH (optimally at pH 5.0-6.5) but not in physiological environment. These two ligands bind to distinct binding sites on the receptor molecule and by different mechanisms. Now, it is known that the expression of FcRn is not restricted to sites involved in the transport of maternal IgG, and this receptor is not responsible only for transfer the passive immunity from mother to the offspring. But FcRn has a much broader range of expression and function, throughout life and in many different cell types and tissues of humans and animals. This review summarizes the status of our knowledge on the expression, interaction with ligands and functions of the neonatal Fc receptor. This article shows also the possibilities of utilizing a current knowledge on FcRn for therapeutic purposes.

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