scholarly journals Role of extracellular mycobacteria in blood-retinal barrier invasion in a zebrafish model of ocular TB

2021 ◽  
Author(s):  
Santhosh Kumar Damera ◽  
Ranjan Kumar Panigrahi ◽  
Sanchita Mitra ◽  
Soumyava Basu
Keyword(s):  
Immune Cells ◽  
Vascular Endothelium ◽  
Intraocular Inflammation ◽  
Post Injection ◽  
Blood Retinal Barrier ◽  
Zebrafish Model ◽  
Course Of Disease ◽  
Retinal Tissue ◽  
Ocular Tb

Intraocular inflammation following mycobacterial dissemination to the eye is common in tuberculosis (TB)-endemic countries. However, the early host-pathogen interactions during ocular dissemination are unknown. In this study, we investigate the early events during mycobacterial invasion of the blood-retinal barriers (BRB) with fluorescent tagged  Mycobacterium marinum  ( Mm ), host macrophages and retinal vasculature in a zebrafish model of ocular TB. We found that  Mm  invaded the vascular endothelium either in extracellular or intracellular (inside phagocytes) state, typically 3-4 days post-injection (dpi). Extracellular  Mm  are phagocytosed in the retinal tissue, and progress to form a compact granuloma around 6 dpi. Intracellular  Mm  crossing the BRB are likely to be less virulent, and either persist inside solitary macrophages (most cases), or progress to loosely arranged granuloma (rare). The early interactions between mycobacteria and host immune cells can thus determine the course of disease during mycobacterial dissemination to the eye.

scholarly journals Role of Extracellular Mycobacteria in Blood-Retinal Barrier Invasion in a Zebrafish Model of Ocular TB

Pathogens ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 333
Author(s):  
Santhosh Kumar Damera ◽  
Ranjan Kumar Panigrahi ◽  
Sanchita Mitra ◽  
Soumyava Basu
Keyword(s):  
Immune Cells ◽  
Vascular Endothelium ◽  
Intraocular Inflammation ◽  
Post Injection ◽  
Blood Retinal Barrier ◽  
Zebrafish Model ◽  
Course Of Disease ◽  
Retinal Tissue ◽  
Ocular Tb

Intraocular inflammation following mycobacterial dissemination to the eye is common in tuberculosis (TB)-endemic countries. However, the early host–pathogen interactions during ocular dissemination are unknown. In this study, we investigated the early events during mycobacterial invasion of the blood-retinal barriers (BRBs) with fluorescent-tagged Mycobacterium marinum (Mm), host macrophages, and retinal vasculature in a zebrafish model of ocular TB. We found that Mm invaded the vascular endothelium in either the extracellular or intracellular (inside phagocytes) state, typically 3–4 days post-injection (dpi). Extracellular Mm are phagocytosed in the retinal tissue and progress to form a compact granuloma around 6 dpi. Intracellular Mm crossing the BRBs are likely to be less virulent and either persist inside solitary macrophages (in most cases) or progress to loosely arranged granuloma (rarely). The early interactions between mycobacteria and host immune cells can thus determine the course of disease during mycobacterial dissemination to the eye.

scholarly journals A Zebrafish Model for Ocular Tuberculosis

2017 ◽  
Author(s):  
Kevin Takaki ◽  
Lalita Ramakrishnan ◽  
Soumyava Basu
Keyword(s):  
Vision Loss ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Tuberculous Infection ◽  
Blood Monocytes ◽  
Blood Retinal Barrier ◽  
Zebrafish Model ◽  
Ocular Tuberculosis ◽  
Department Of Health ◽  
Ocular Tb

AbstractOcular tuberculosis (TB) commonly causes severe inflammation and vision loss in TB-endemic countries. The mechanism by which tuberculous infection becomes established in the eye is poorly understood. We used Mycobacterium marinum-infected zebrafish larvae to study the early pathogenesis of ocular TB and found hematogenous bacterial seeding of the eye despite a functional blood retinal barrier. Prototypical early granulomas formed that involved the retinal vasculature and retinal pigment epithelium-choroid complex; characteristic locations for human ocular TB. Peripheral blood monocytes were recruited to the growing granuloma suggesting that the immune privileged nature of the eye is breached by this inflammatory focus.Conflict of interestnone disclosedFundingThis work was supported in part by a ‘Short-term fellowship’ to SB by Department of Health Research, Government of India.

scholarly journals Role of glycolysis in retinal vascular endothelium, glia, pigment epithelium, and photoreceptor cells and as therapeutic targets for related retinal diseases

2021 ◽  
Vol 14 (9) ◽  
pp. 1302-1309
Author(s):  
Ting-Ting Yang ◽  
◽  
Li-Jie Dong ◽  
Keyword(s):  
Vascular Endothelium ◽  
Vision Loss ◽  
Cell Function ◽  
Aerobic Glycolysis ◽  
Pigment Epithelium ◽  
Photoreceptor Cells ◽  
Blood Retinal Barrier ◽  
Inhibition Of Glycolysis ◽  
Short Time

Glycolysis produces large amounts of adenosine triphosphate (ATP) in a short time. The retinal vascular endothelium feeds itself primarily through aerobic glycolysis with less ATP. But when it generates new vessels, aerobic glycolysis provides rapid and abundant ATP support for angiogenesis, and thus inhibition of glycolysis in endothelial cells can be a target for the treatment of neovascularization. Aerobic glycolysis has a protective effect on Müller cells, and it can provide with a target for visual protection and maintenance of the blood-retinal barrier. Under physiological conditions, the mitochondria of RPE can use lactic acid produced by photoreceptor cells as an energy source to provide ATP for survival. In pathological conditions, because RPE cells avoid their oxidative damage by increasing glycolysis, a large number of glycolysis products accumulate, which in turn has a toxic effect on photoreceptor cells. This shows that stabilizing the function of RPE mitochondria may become a target for the treatment of diseases such as retinal degeneration. The decrease of aerobic glycolysis leads to the decline of photoreceptor cell function and impaired vision; therefore, aerobic glycolysis of stable photoreceptor cells provides a reliable target for delaying vision loss. It is of great significance to study the role of glycolysis in various retinal cells for the targeted treatment of ocular fundus diseases.

Role of FLT3 gene mutations in acute myeloid leukemia: effect on course of disease and results of therapy

2019 ◽  
Vol XIV (1) ◽  
Author(s):  
A.M. Radzhabova ◽  
S.V. Voloshin ◽  
I.S. Martynkevich ◽  
A.A. Kuzyaeva ◽  
V.A. Shuvaev ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Gene Mutations ◽  
Course Of Disease ◽  
Acute Myeloid

PD-L1 Inhibitors for the Treatment of Prostate Cancer

2020 ◽  
Vol 21 (15) ◽  
pp. 1558-1565
Author(s):  
Matteo Santoni ◽  
Francesco Massari ◽  
Liang Cheng ◽  
Alessia Cimadamore ◽  
Marina Scarpelli ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trials ◽  
T Lymphocytes ◽  
Chronic Inflammation ◽  
Immune Cells ◽  
Response To Therapy ◽  
Complex Series

The carcinogenesis of prostate cancer (PCa) results from a complex series of events. Chronic inflammation and infections are crucial in this context. Infiltrating M2 type macrophages, as well as neutrophils and T lymphocytes, contribute to PCa development, progression and response to therapy. The preliminary findings on the efficacy of immunotherapy in patients with PCa were not encouraging. However, a series of studies investigating anti-PD-L1 agents such as Atezolizumab, Avelumab and Durvalumab used alone or in combination with other immunotherapies, chemotherapy or locoregional approaches are in course in this tumor. In this review, we illustrate the role of immune cells and PD-L1 expression during PCa carcinogenesis and progression, with a focus on ongoing clinical trials on anti-PD-L1 agents in this context.

scholarly journals AB0676 THE ROLE OF ACPA AND ANA IN SPONDYLOARTHRITIS: HOW THE AUTOIMMUNE DYSREGULATION CAN AFFECT THE COURSE OF DISEASE AND THERAPEUTIC SUCCESS OF MONOTHERAPY DMARDS AND bDMARDs

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1633.1-1633
Author(s):  
D. Cici ◽  
C. Rotondo ◽  
A. Corrado ◽  
S. Berardi ◽  
N. Mansueto ◽  
...  
Keyword(s):  
Psoriatic Arthritis ◽  
Start Time ◽  
Disease Manifestation ◽  
Therapeutic Success ◽  
Course Of Disease ◽  
Drug Survival ◽  
Comorbidity Index ◽  
Citrullinated Protein ◽  
Axial Involvement

Background:Occasional findings of anti-citrullinated-protein-antibodies (ACPA) and anti-nuclear-antibodies (ANA) were rarely described in literature on Psoriatic Arthritis (PsA) and on Spondyloarthritis (SpA) in general. How these autoimmune dysregulations can affect the course of them is not yet understood.Objectives:The aim of our study is to evaluate if the presence of ACPA and ANA can determine different disease subsets and influence the DMARDs monotherapy (methotrexate) drug survival (DSM) and b-DMARDs multi-failure patients (MF).Methods:We conducted a retrospective study on patients with Psoriatic Arthritis (PsA) and Spondyloarthritis that fulfilled the ASAS and CASPAR criteria. Patients with diagnosis of connective tissue disease and rheumatoid arthritis and patients ≤ 18 years old were excluded from the study. For each patient, the following variables were considered: age, ACPA, ANA, time between arthritis onset and start of DMARDs (start-time), DSM, switch to b-DMARDs (sw-bDMARDs), arthritis subset (oligoarticular (OA), polyarticular (PA), enthesitis (EA), axial involvement (AI)), number of comorbidities (NC), Charlson Comorbidity Index (CCI).Results:150 patients (55% with PsA and 45% with another SpA) were included in the study. No differences were found in age, ANA rate, ACPA rate, start-time, OA, PA, EA, AI, NC and CCI between the PsA and SpA groups.In the whole group of patients, the ACPA+ subjects(11%) had a significant increase of NC (2.47 ± 1.5 vs 1.6 ± 1.4, p=0.035), a trend to higher CCI, to switch to b-DMARDs, and to be MF compared to those without ACPA. In the same group, the ANA+ patients (12%) showed shorter DSM (233.5 wk ± 45.9 vs 548.0 wk ± 56.8, p=0.362) with similar trend in each subgroup (PsA and SpA).In SpA group, the ACPA+ patients(6,3%) had a trend to shorter DSM (269.0 weeks ± 125vs 603.96 wk± 92.8, p=0.492),to higher sw-bDMARDs, and to be MF, higher NC and CCI compared to those without ACPA. No differences in clinical subset (OA, PA, EA, AI) were observed. In the same group the ANA+ patients had significant higher rate of PA (100% vs 65%, p=0.026) rather than OA (0% vs 35%, p=0.025). No significant differences were found in NC, CCI, MF.In the PsA group, ACPA+ patients showed a trend to develop PA and EA subsets, shorter DSM (187.5 wk ± 48.7 vs 299.6 wk ± 31.4, p=0.415), higher rate to sw-bDMARDs and to be MF. The ANA+ PsA patients had higher trend to develop PA and AI subsets rather than OA and EA. All ANA+ patients were MF (100% vs 42%, p=0.046).Conclusion:The ACPA and ANA positivity in PsA and SpA patients could be suggestive of more severe clinical disease manifestation, higher frequency of comorbidities and lower predicted 10-year survival (CCI). Moreover, this autoimmune dysregulation could be associated with worse drug survival in monotherapy with methotrexate and higher chance to be MF. Therefore, they can be taken into account for clinical management of these patients.Disclosure of Interests:None declared

The Role of α7nAChR-Mediated Cholinergic Anti-inflammatory Pathway in Immune Cells

Inflammation ◽  
2021 ◽  
Author(s):  
Yi-jin Wu ◽  
Li Wang ◽  
Chao-fan Ji ◽  
Shao-fei Gu ◽  
Qin Yin ◽  
...  
Keyword(s):  
Immune Cells ◽  
Inflammatory Pathway ◽  
Anti Inflammatory

Prevention of Dextran Sulfate Sodium-induced Mouse Colitis by a Fungal Protein Ling Zhi-8 via Promoting the Barrier Function of Intestinal Epithelial Cells

2021 ◽  
Author(s):  
Yu-Huan Chen ◽  
Jenn-Yeu Shin ◽  
Hsiu-Mei Wei ◽  
Chi-Chen Lin ◽  
Linda Chia-Hui Yu ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Immune Cells ◽  
Ganoderma Lucidum ◽  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Intestinal Epithelial Cells ◽  
Intestinal Epithelial ◽  
Fungal Protein ◽  
Fungal Immunomodulatory Protein

A fungal immunomodulatory protein Ling Zhi-8 (LZ-8) isolated from Ganoderma lucidum (GL) regulates immune cells and inhibits tumor growth; however, the role of LZ-8 in intestinal epithelial cells (IECs) is...

scholarly journals Microfluidic tumor-on-a-chip model to evaluate the role of tumor environmental stress on NK cell exhaustion

2021 ◽  
Vol 7 (8) ◽  
pp. eabc2331 ◽  
Author(s):  
Jose M. Ayuso ◽  
Shujah Rehman ◽  
Maria Virumbrales-Munoz ◽  
Patrick H. McMinn ◽  
Peter Geiger ◽  
...  
Keyword(s):  
Nk Cells ◽  
Immune Cells ◽  
Molecular Mechanisms ◽  
Nk Cell ◽  
Checkpoint Inhibitors ◽  
Waste Product ◽  
Extended Period ◽  
Cell Exhaustion

Solid tumors generate a suppressive environment that imposes an overwhelming burden on the immune system. Nutrient depletion, waste product accumulation, hypoxia, and pH acidification severely compromise the capacity of effector immune cells such as T and natural killer (NK) cells to destroy cancer cells. However, the specific molecular mechanisms driving immune suppression, as well as the capacity of immune cells to adapt to the suppressive environment, are not completely understood. Thus, here, we used an in vitro microfluidic tumor-on-a-chip platform to evaluate how NK cells respond to the tumor-induced suppressive environment. The results demonstrated that the suppressive environment created by the tumor gradually eroded NK cell cytotoxic capacity, leading to compromised NK cell surveillance and tumor tolerance. Further, NK cell exhaustion persisted for an extended period of time after removing NK cells from the microfluidic platform. Last, the addition of checkpoint inhibitors and immunomodulatory agents alleviated NK cell exhaustion.

scholarly journals RhoA- and Actin-Dependent Functions of Macrophages from the Rodent Cardiac Transplantation Model Perspective -Timing Is the Essence

Biology ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 70
Author(s):  
Malgorzata Kloc ◽  
Ahmed Uosef ◽  
Martha Villagran ◽  
Robert Zdanowski ◽  
Jacek Z. Kubiak ◽  
...  
Keyword(s):  
Immune Response ◽  
Circadian Rhythm ◽  
Immune Cells ◽  
Chronic Rejection ◽  
Cardiac Transplantation ◽  
Small Gtpase ◽  
Eukaryotic Cells ◽  
Transplantation Model

The small GTPase RhoA, and its down-stream effector ROCK kinase, and the interacting Rac1 and mTORC2 pathways, are the principal regulators of the actin cytoskeleton and actin-related functions in all eukaryotic cells, including the immune cells. As such, they also regulate the phenotypes and functions of macrophages in the immune response and beyond. Here, we review the results of our and other’s studies on the role of the actin and RhoA pathway in shaping the macrophage functions in general and macrophage immune response during the development of chronic (long term) rejection of allografts in the rodent cardiac transplantation model. We focus on the importance of timing of the macrophage functions in chronic rejection and how the circadian rhythm may affect the anti-chronic rejection therapies.

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