Brain Granulomas in Neurocysticercosis Patients Are Associated with a Th1 and Th2 Profile

ABSTRACT Neurocysticercosis (NCC) is a common central nervous system (CNS) infection caused by Taenia solium metacestodes. Despite the well-documented importance of the granulomatous response in the pathogenesis of this infection, there is limited information about the types of cells and cytokines involved. In fact, there has been limited characterization of human brain granulomas with any infectious agent. In the present study a detailed histological and immunohistochemical analysis of the immune response was performed on eight craniotomy specimens where a granuloma surrounded each T. soliummetacestode. The results indicated that in all the specimens there was a dying parasite surrounded by a mature granuloma with associated fibrosis, angiogenesis, and an inflammatory infiltrate. The most abundant cell types were plasma cells, B and T lymphocytes, macrophages, and mast cells. Th1 cytokines were prevalent and included gamma interferon, interleukin-18 (IL-18), and the immunosuppressive, fibrosis-promoting cytokine transforming growth factor β. The Th2 cytokines IL-4, IL-13, and IL-10 were also present. These observations indicate that a chronic immune response is elicited in the CNS environment with multiple cell types that together secrete inflammatory and anti-inflammatory cytokines. In addition, both collagen type I and type III deposits were evident and could contribute to irreversible nervous tissue damage in NCC patients.

Download Full-text

Myostatin/Activin-A Signaling in the Vessel Wall and Vascular Calcification

Cells ◽

10.3390/cells10082070 ◽

2021 ◽

Vol 10 (8) ◽

pp. 2070

Author(s):

Pasquale Esposito ◽

Daniela Verzola ◽

Daniela Picciotto ◽

Leda Cipriani ◽

Francesca Viazzi ◽

...

Keyword(s):

Vascular Calcification ◽

Intracellular Signaling ◽

Transforming Growth Factor ◽

Vascular Inflammation ◽

Transforming Growth Factor Β ◽

Cell Types ◽

Activin A ◽

Premature Aging ◽

High Morbidity ◽

Type I

A current hypothesis is that transforming growth factor-β signaling ligands, such as activin-A and myostatin, play a role in vascular damage in atherosclerosis and chronic kidney disease (CKD). Myostatin and activin-A bind with different affinity the activin receptors (type I or II), activating distinct intracellular signaling pathways and finally leading to modulation of gene expression. Myostatin and activin-A are expressed by different cell types and tissues, including muscle, kidney, reproductive system, immune cells, heart, and vessels, where they exert pleiotropic effects. In arterial vessels, experimental evidence indicates that myostatin may mostly promote vascular inflammation and premature aging, while activin-A is involved in the pathogenesis of vascular calcification and CKD-related mineral bone disorders. In this review, we discuss novel insights into the biology and physiology of the role played by myostatin and activin in the vascular wall, focusing on the experimental and clinical data, which suggest the involvement of these molecules in vascular remodeling and calcification processes. Moreover, we describe the strategies that have been used to modulate the activin downward signal. Understanding the role of myostatin/activin signaling in vascular disease and bone metabolism may provide novel therapeutic opportunities to improve the treatment of conditions still associated with high morbidity and mortality.

Download Full-text

Nodal signalling and apoptosis

Reproduction ◽

10.1530/rep-07-0053 ◽

2007 ◽

Vol 133 (5) ◽

pp. 847-853 ◽

Cited By ~ 31

Author(s):

Hongmei Wang ◽

Benjamin K Tsang

Keyword(s):

Transforming Growth Factor ◽

Biological Effects ◽

Transforming Growth Factor Β ◽

Cell Types ◽

Type I ◽

Type Ii ◽

Human Trophoblast ◽

Adult Tissues ◽

Ovarian Epithelial Cancer ◽

Smad Proteins

Nodal, a member of the transforming growth factor β family, was first cloned from a 7.5 day post-coitum mouse embryo cDNA library. Nodal exerts its biological effects by signalling through its types I and II serine/threonine kinase receptor complex and intracellular Smad proteins. The type II receptors for Nodal are Activin type II receptors ActRIIA and ActRIIB, whereas the putative type I receptors are Activin receptor like kinase (ALK) 4 and ALK7. The main Smad proteins involved in Nodal signalling are Smad2 and Smad3. Studies of Nodal in adult tissues indicate that it is pro-apoptotic in rat ovarian granulosa cells, human trophoblast cells and human ovarian epithelial cancer cells and is growth inhibitory in the latter two cell types. This review summarises the progress made on the functions of Nodal in the apoptosis of adult tissues, especially in the ovary and placenta.

Download Full-text

PGE2 Displays Immunosuppressive Effects During Human Active Tuberculosis

10.21203/rs.3.rs-199608/v1 ◽

2021 ◽

Author(s):

Joaquín Pellegrini ◽

Candela Martin ◽

María Paula Morelli ◽

Julieta Aylen Schander ◽

Nancy Liliana Tateosian ◽

...

Keyword(s):

Immune Response ◽

Surface Expression ◽

Lipid Mediator ◽

Type I ◽

Limited Information ◽

Chronic Infections ◽

Human Host ◽

Tb Treatment ◽

Attractive Therapeutic Target ◽

Immunosuppressive Action

Abstract Prostaglandin E2 (PGE2), an active lipid compound derived from arachidonic acid, regulates different stages of the immune response of the host during several pathologies such as chronic infections or cancer. In fact, manipulation of PGE2 levels was proposed as an approach for countering the Type I IFN signature of tuberculosis (TB). However, very limited information regarding the PGE2 pathway in patients with active TB is currently available. In the present work, we demonstrated that PGE2 exerts a potent immunosuppressive action during the immune response of the human host against Mycobacterium tuberculosis (Mtb) infection. Actually, we showed that PGE2 significantly reduced lymphoproliferation, the production of proinflammatory cytokines, and the surface expression of several immunological receptors. On the other hand, PGE2 promoted autophagy in monocytes and neutrophils cultured with Mtb antigens. These results suggest that PGE2 might be attenuating the excessive inflammatory immune response caused by Mtb, emerging as an attractive therapeutic target. Taken together, our findings contribute to the knowledge of the role of PGE2 in the human host resistance to Mtb and highlight the potential of this lipid mediator as a tool to improve anti-TB treatment.

Download Full-text

A Immunohistochemical Analysis of a Rat Model of Proliferative Vitreoretinopathy and a Comparison of the Expression of Tgf-Β and PDGF Among the Induction Methods

Bosnian Journal of Basic Medical Sciences ◽

10.17305/bjbms.2010.2686 ◽

2010 ◽

Vol 10 (3) ◽

pp. 204-209 ◽

Cited By ~ 17

Author(s):

Xiao-Zhi Zheng ◽

Lian-Fang Du ◽

Hui-Ping Wang

Keyword(s):

Growth Factor ◽

Proliferative Vitreoretinopathy ◽

Transforming Growth Factor ◽

Platelet Rich Plasma ◽

Immunohistochemical Analysis ◽

Wistar Rat ◽

Cell Types ◽

Enzyme Linked Immunosorbent Assay ◽

Experimental Proof ◽

Expression Levels

Proliferative vitreoretinopathy (PVR) is a serious complication of retinal detachment surgery or ocular trauma. Our previous study indicated that intravitreal co-injection of retinal pigmented epithelial (RPE) -J cells and platelet-rich plasma (PRP) (not RPE-J cells or PRP alone) in Wistar rat eyes can successfully induce a model of PVR. But which cells are involved in this process and why different induction methods, intravitreal injection of RPE-J cells or/and PRP, induced a different situation remain to be unknown. In this study, immunohistochemistry was performed to identify the main cell types involved in this process. The expression levels of transforming growth factor (TGF) -β2, platelet-derived growth factor (PDGF)- AA and PDGF-BB were tested using enzyme-linked immunosorbent assay (ELISA)The results showed that RPE cells, glial cells, fibroblasts and macrophages took part in the pathogenesis of this model. The expression levels and durations of TGF^2 and PDGF-BB partially explained the different results induced by the different induction methods. This provides an experimental proof for attenuation of the experimental PVR by targeting at a specific cells or growth factor.

Download Full-text

Landscape of glioblastoma niches reveals the prognostic effects of tumor-infiltrating cells

10.1101/2021.01.20.427411 ◽

2021 ◽

Author(s):

Zixuan Xiao ◽

Wei Zhang ◽

Guanzhang Li ◽

Wendong Li ◽

Lin Li ◽

...

Keyword(s):

Immune Response ◽

T Cells ◽

Tumor Cell ◽

Cd8 T Cells ◽

Plasma Cells ◽

Cell Types ◽

Enrichment Score ◽

Large Gene ◽

Mesenchymal Differentiation ◽

Positive Immune Response

AbstractA comprehensive characterization of non-tumor cells in the niches of primary glioblastoma is not fully established yet. This study aims to present an overview of tumor-infiltrating non-malignant cells in the complex microenvironment of glioblastoma with detailed characterizations of their prognostic effects. We curate 540 gene signatures covering a total of 64 non-tumor cell types. Cell type-specific expression patterns are interrogated by normalized enrichment score (NES) across four large gene expression profiling cohorts of glioblastoma with a total number of 967 cases. The GBMs in each cohort are hierarchically clustered into negative or positive immune response classes with significantly different overall survival. Our results show that astrocytes, macrophages, monocytes, NKTs, preadipocytes, smooth muscle cells, and MSC are risk factors, while CD8 T cells, CD8+ T cells, and plasma cells are protective factors. Moreover, we find that the immune system and organogenesis are uniformly enriched in negative immune response clusters, in contrast to the enrichment of nervous system in positive immune response clusters. Mesenchymal differentiation is also observed in the negative immune response clusters. High enrichment status of macrophages in negative immune response clusters are independently validated by analyzing scRNA-seq data from eight high-grade gliomas, revealing that negative immune response samples comprised 46.63% to 55.12% of macrophages, whereas positive immune response samples comprised only 1.70% to 8.12%, with IHC staining of samples from six short-term and six long-term survivors of GBMs confirming the results.Simple SummaryThe landscape of infiltrating non-tumor cells in glioblastoma niches remains unclear. In this study, we explore the enrichment status of a total of 64 non-tumor cell types predicted by applying 540 gene signatures curated from literature and normalized enrichment score (NES) across four large gene expression profiling cohorts of glioblastoma with 967 cases. Based on non-tumor cell type-based enrichment status, GBMs in each cohort are classified into positive or negative immune response clusters, showing a statistically significant different overall survival. Astrocytes, macrophages, monocytes, NKTs, preadipocytes, smooth muscle cells, and MSC are identified as risk factors, as well as protector factors of CD8 T cells, CD8+ T cells, and plasma cells. Our results also find that immune system- and organogenesis-related GO terms are uniformly enriched in negative immune response clusters, whereas positive immune response clusters are enriched with GO terms concerning the nervous system. The mesenchymal differentiation is observed in the negative immune response clusters. Particularly, the high presence of macrophages in the negative immune response clusters is further validated using scRNA-seq analysis and IHC staining of GBMs from independent cohorts.

Download Full-text

Immune Response in Severe and Non-Severe Coronavirus Disease 2019 (COVID-19) Infection: A Mechanistic Landscape

Frontiers in Immunology ◽

10.3389/fimmu.2021.738073 ◽

2021 ◽

Vol 12 ◽

Author(s):

Kavitha Mukund ◽

Priya Nayak ◽

Chethan Ashokkumar ◽

Sohail Rao ◽

Jose Almeda ◽

...

Keyword(s):

Immune Response ◽

Immune Cell ◽

Severe Disease ◽

Cell Types ◽

Cellular Heterogeneity ◽

Type I ◽

Γδt Cells ◽

Mait Cells ◽

Integrative Analyses ◽

Severe Infections

The mechanisms underlying the immune remodeling and severity response in coronavirus disease 2019 (COVID-19) are yet to be fully elucidated. Our comprehensive integrative analyses of single-cell RNA sequencing (scRNAseq) data from four published studies, in patients with mild/moderate and severe infections, indicate a robust expansion and mobilization of the innate immune response and highlight mechanisms by which low-density neutrophils and megakaryocytes play a crucial role in the cross talk between lymphoid and myeloid lineages. We also document a marked reduction of several lymphoid cell types, particularly natural killer cells, mucosal-associated invariant T (MAIT) cells, and gamma-delta T (γδT) cells, and a robust expansion and extensive heterogeneity within plasmablasts, especially in severe COVID-19 patients. We confirm the changes in cellular abundances for certain immune cell types within a new patient cohort. While the cellular heterogeneity in COVID-19 extends across cells in both lineages, we consistently observe certain subsets respond more potently to interferon type I (IFN-I) and display increased cellular abundances across the spectrum of severity, as compared with healthy subjects. However, we identify these expanded subsets to have a more muted response to IFN-I within severe disease compared to non-severe disease. Our analyses further highlight an increased aggregation potential of the myeloid subsets, particularly monocytes, in COVID-19. Finally, we provide detailed mechanistic insights into the interaction between lymphoid and myeloid lineages, which contributes to the multisystemic phenotype of COVID-19, distinguishing severe from non-severe responses.

Download Full-text

Increased Accumulation of Regulatory Granulocytic Myeloid Cells in Mannose Receptor C Type 1-Deficient Mice Correlates with Protection in a Mouse Model of Neurocysticercosis

Infection and Immunity ◽

10.1128/iai.01176-12 ◽

2013 ◽

Vol 81 (4) ◽

pp. 1052-1063 ◽

Cited By ~ 10

Author(s):

Pramod Kumar Mishra ◽

Elizabeth G. Morris ◽

Jenny A. Garcia ◽

Astrid E. Cardona ◽

Judy M. Teale

Keyword(s):

Immune Response ◽

Mouse Model ◽

Immune Cell ◽

Critical Role ◽

Taenia Solium ◽

Mannose Receptor ◽

Cns Infection ◽

Lectin Receptors ◽

Content Type

ABSTRACTNeurocysticercosis (NCC) is a central nervous system (CNS) infection caused by the metacestode stage of the parasiteTaenia solium. During NCC, the parasites release immunodominant glycan antigens in the CNS environment, invoking immune responses. The majority of the associated pathogenesis is attributed to the immune response against the parasites. Glycans from a number of pathogens, including helminths, act as pathogen-associated molecular pattern molecules (PAMPs), which are recognized by pattern recognition receptors (PRRs) known as C-type lectin receptors (CLRs). Using a mouse model of NCC by infection with the related parasiteMesocestoides corti, we have investigated the role of mannose receptor C type 1 (MRC1), a CLR which recognizes high-mannose-containing glycan antigens. Here we show that MRC1−/−mice exhibit increased survival times after infection compared with their wild-type (WT) counterparts. The decreased disease severity correlates with reduced levels of expression of markers implicated in NCC pathology, such as interleukin-1β (IL-1β), IL-6, CCL5, and matrix metalloproteinase 9 (MMP9), in addition to induction of an important repair marker, fibroblast growth factor 2 (FGF2). Furthermore, the immune cell subsets that infiltrate the brain of MRC1−/−mice are dramatically altered and characterized by reduced numbers of T cells and the accumulation of granulocytic cells with an immune phenotype resembling granulocytic myeloid-dependent suppressor cells (gMDSCs). The results suggest that MRC1 plays a critical role in myeloid plasticity, which in turn affects the adaptive immune response and immunopathogenesis during murine NCC.

Download Full-text

Immunohistochemical Assessment of Immune Response in the Dermis of Sarcoptes scabiei—Infested Wild Carnivores (Wolf and Fox) and Ruminants (Chamois and Red Deer)

Animals ◽

10.3390/ani10071146 ◽

2020 ◽

Vol 10 (7) ◽

pp. 1146

Author(s):

Ileana Z. Martínez ◽

Álvaro Oleaga ◽

Irene Sojo ◽

María José García-Iglesias ◽

Claudia Pérez-Martínez ◽

...

Keyword(s):

Immune Response ◽

T Lymphocytes ◽

B Lymphocytes ◽

Red Deer ◽

Plasma Cells ◽

Inflammatory Cells ◽

Sarcoptes Scabiei ◽

Type I ◽

Effective Response ◽

Wild Mammals

Sarcoptic mange is caused by the mite Sarcoptes scabiei and has been described in several species of domestic and wild mammals. Macroscopic lesions are predominantly hyperkeratotic (type I hypersensitivity) in fox, chamois and deer, but alopecic (type IV hypersensitivity) in wolf and some fox populations. To begin to understand the immune processes underlying these species differences in lesions, we examined skin biopsies from wolves (Canis lupus), foxes (Vulpes vulpes), chamois (Rupicapra rupicapra) and red deer (Cervus elaphus) naturally infested with S. scabiei. Twenty skin samples from five animals per species were used. Sections were immuno-stained with primary antibodies against Iba1 to detect macrophages, lambda chain to detect plasma cells, CD3 to detect T lymphocytes and CD20 to detect B lymphocytes. Skin lesions contained significantly more inflammatory cells in the fox than in the wolf and chamois. Macrophages were the most abundant inflammatory cells in the lesions of all the species studied, suggesting a predominantly innate, non-specific immune response. Lesions from the wolf contained higher proportions of macrophages than the other species, which may reflect a more effective response, leading to alopecic lesions. In red deer, macrophages were significantly more abundant than plasma cells, T lymphocytes and B lymphocytes, which were similarly abundant. The fox proportion of plasma cells was significantly higher than those of T and B lymphocytes. In chamois, T lymphocytes were more abundant than B lymphocytes and plasma cells, although the differences were significant only in the case of macrophages. These results suggest that all the species examined mount a predominantly innate immune response against S. scabiei infestation, while fox and chamois may also mount substantial humoral and cellular immune responses, respectively, with apparently scarce effectiveness that lead to hyperkeratotic lesions.

Download Full-text

Multiomics Analysis Reveals the Prognostic Non-tumor Cell Landscape in Glioblastoma Niches

Frontiers in Genetics ◽

10.3389/fgene.2021.741325 ◽

2021 ◽

Vol 12 ◽

Author(s):

Zixuan Xiao ◽

Wei Zhang ◽

Guanzhang Li ◽

Wendong Li ◽

Lin Li ◽

...

Keyword(s):

Immune Response ◽

T Cells ◽

Tumor Cell ◽

Plasma Cells ◽

Expression Patterns ◽

Cell Types ◽

Enrichment Score ◽

Specific Expression ◽

Primary Glioblastoma ◽

Positive Immune Response

A comprehensive characterization of non-tumor cells in the niches of primary glioblastoma is not fully established yet. This study aims to present an overview of non-malignant cells in the complex microenvironment of glioblastoma with detailed characterizations of their prognostic effects. We curate 540 gene signatures covering a total of 64 non-tumor cell types. Cell type-specific expression patterns are interrogated by normalized enrichment score across four large gene expression profiling cohorts of glioblastoma with a total number of 967 cases. The glioblastoma multiforms (GBMs) in each cohort are hierarchically clustered into negative or positive immune response classes with significantly different overall survival. Our results show that astrocytes, macrophages, monocytes, NKTs, and MSC are risk factors, while CD8 T cells, CD8 naive T cells, and plasma cells are protective factors. Moreover, we find that the immune system and organogenesis are uniformly enriched in negative immune response clusters, in contrast to the enrichment of nervous system in positive immune response clusters. Mesenchymal differentiation is also observed in the negative immune response clusters. High enrichment status of macrophages in negative immune response clusters is independently validated by analyzing scRNA-seq data from eight high-grade gliomas, revealing that negative immune response samples comprised 46.63 to 55.12% of macrophages, whereas positive immune response samples comprised only 1.70 to 8.12%, with IHC staining of samples from six short-term and six long-term survivors of GBMs confirming the results.

Download Full-text

Immunosuppressive role of PGE2 during human tuberculosis

10.1101/2020.08.04.236257 ◽

2020 ◽

Author(s):

Joaquín Miguel Pellegrini ◽

Nancy Liliana Tateosian ◽

María Paula Morelli ◽

Agustín Rollandelli ◽

Nicolás Oscar Amiano ◽

...

Keyword(s):

Immune Response ◽

Surface Expression ◽

Lipid Mediator ◽

Autophagic Flux ◽

Type I ◽

Limited Information ◽

Chronic Infections ◽

Tb Treatment ◽

Attractive Therapeutic Target ◽

Immunosuppressive Action

Prostaglandin E2 (PGE2), an active lipid compound derived from arachidonic acid, regulates different stages of the immune response of the host during several pathologies such as chronic infections or cancer. Manipulation of PGE2 levels was proposed as an approach for countering the Type I IFN signature of tuberculosis (TB), but very limited information exists about this pathway in patients with active TB. Here, we demonstrated that PGE2 exerts a potent immunosuppressive action during the immune response of the human host against M. tuberculosis. Thus, we showed that PGE2 inhibited both lymphoproliferation and cytokine production of proinflammatory cytokines, together with a significant reduction of the surface expression of several immunological receptors in human cells. However, PGE2 promoted the autophagic flux of antigen-stimulated monocytes, even in the presence of IFNα. In this way, the attenuation of inflammation and immunopathology caused by an excessive immune response emerges as an attractive therapeutic target. Together, our findings contribute to the knowledge of Mtb-resistance mediated by PGE2 and highlight the potential of this lipid mediator as a tool to improve anti-TB treatment.

Download Full-text