VEGF-A from Granuloma Macrophages Regulates Granulomatous Inflammation by a Non-angiogenic Pathway during Mycobacterial Infection

Publication date: 14 May 2019Source: Cell Reports, Volume 27, Issue 7Author(s): Jeffrey S. Harding, Melinda Herbath, Yuli Chen, Aditya Rayasam, Anna Ritter, Balazs Csoka, George Hasko, Iacovos P. Michael, Zsuzsanna Fabry, Andras Nagy, Matyas SandorSummaryMany autoimmune and infectious diseases are characterized by the formation of granulomas which are inflammatory lesions that consist of spatially organized immune cells. These sites protect the host and control pathogens like Mycobacterium tuberculosis (Mtb), but are highly inflammatory and cause pathology. Using bacille Calmette-Guerin (BCG) and Mtb infection in mice that induce sarcoid or caseating granulomas, we show that a subpopulation of granuloma macrophages produces vascular endothelial growth factor (VEGF-A), which recruits immune cells to the granuloma by a non-angiogenic pathway. Selective blockade of VEGF-A in myeloid cells, combined with granuloma transplantation, shows that granuloma VEGF-A regulates granulomatous inflammation. The severity of granuloma-related inflammation can be ameliorated by pharmaceutical or genetic inhibition of VEGF-A, which improves survival of mice infected with virulent Mtb without altering host protection. These data show that VEGF-A inhibitors could be used as a host-directed therapy against granulomatous diseases like tuberculosis and sarcoidosis, thereby expanding the value of already existing and approved anti-VEGF-A drugs.Graphical Abstract
Source: Cell Reports - Category: Cytology Source Type: research

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Authors: Neiter E, Conart JB, Baumann C, Rousseau H, Zuily S, Angioi-Duprez K Abstract INTRODUCTION: The purpose of this study was to describe the epidemiologic characteristics of adult uveitis evaluated at the regional center of excellence specializing in systemic and autoimmune disease in the Nancy university medical center. The secondary objectives were to describe the progression over time of the various etiologies and to identify local specificities. MATERIALS AND METHODS: We performed a retrospective epidemiological study of patients diagnosed with uveitis. All patients were referred to the regional cente...
Source: Journal Francais d Ophtalmologie - Category: Opthalmology Tags: J Fr Ophtalmol Source Type: research
Discussion Facial nerve palsy has been known for centuries, but in 1821 unilateral facial nerve paralysis was described by Sir Charles Bell. Bell’s palsy (BP) is a unilateral, acute facial paralysis that is clinically diagnosed after other etiologies have been excluded by appropriate history, physical examination and/or laboratory testing or imaging. Symptoms include abnormal movement of facial nerve. It can be associated with changes in facial sensation, hearing, taste or excessive tearing. The right and left sides are equally affected but bilateral BP is rare (0.3%). Paralysis can be complete or incomplete at prese...
Source: PediatricEducation.org - Category: Pediatrics Authors: Tags: Uncategorized Source Type: news
​Seventy-five percent of trauma injuries involve some kind of thoracic insult, a quarter of which need a procedural intervention like a chest tube. (Surg Clin North Am 2007;87[1]:95; http://bit.ly/2HaoX90.) Long-term illness, lung disease, and post-operative complications may cause pleural effusions or a pneumothorax, so treating these conditions quickly can significantly decrease patient morbidity and mortality. Other indications for chest tube placement include:Trauma: Pneumothorax, hemopneumothorax, or tension pneumothoraxLong-term illness: Pleural effusion (cancer, pneumonia)Infection: Empyema, purulent pleuriti...
Source: The Procedural Pause - Category: Emergency Medicine Tags: Blog Posts Source Type: blogs
AbstractClinical and radiological features of tuberculosis and sarcoidosis are quite overlapping, and therefore, a diagnostic dilemma often persists. There are no commonly accepted criteria for the diagnosis of sarcoidosis due to the lack of data on the etiology of the disease. The exclusion of tuberculosis in every patient with suspected sarcoidosis is a mandatory stage of diagnosis, especially in countries with a high burden of tuberculosis. A prospective study was conducted with two groups of patients: group I (n = 50)—patients with pulmonary sarcoidosis established according to standard criteria; gr...
Source: Immunologic Research - Category: Allergy & Immunology Source Type: research
ConclusionOur study shows a wide diversity of etiologies of LE in Morocco with essentially an acute mode of onset of symptoms.
Source: Brain and Behavior - Category: Neurology Authors: Tags: ORIGINAL RESEARCH Source Type: research
We present here preliminary descriptive data on the patients' characteristics and their established diagnosis at follow-up.Methods: Since 2015, all patients aged ≥15 years and referred to the hematology or internal medicine department in 117 French hospitals, with an unexplained SM diagnosis (confirmed by echography or CT-scan with a craniocaudal length ≥13 cm) have been invited to participate. Unexplained cause of SM was defined as a first negative clinical workup based on patient's interview and physical examination, and biological routine tests (including complete blood and reticulocytes count, clotting test, live...
Source: Blood - Category: Hematology Authors: Tags: 903. Outcomes Research-Non-Malignant Hematology: Poster III Source Type: research
Granulomatous myopathy is a clinically and etiologically heterogeneous group of uncommon inflammatory myopathies, pathologically characterized by the presence of granulomas in skeletal muscle. Granulomas may contain necrosis as typically seen in infectious disorders (fungal, tuberculosis, or brucellosis) [1-3] or may occur without necrosis, so-called non-necrotizing or non-caseating granulomas. Various disorders were reported in association with non-caseating granulomatous myopathy, including sarcoidosis and less commonly other autoimmune diseases (Crohn's disease, anti-mitochondrial autoimmunity with or without primary bi...
Source: Neuromuscular Disorders - Category: Neurology Authors: Source Type: research
ConclusionsPatients presenting with body weakness need serum potassium estimation. Acquired Bartter ’s syndrome although rare, should be ruled out in those with hypokalemia and metabolic alkalosis with increased urinary potassium loss with poor response to potassium replacement.
Source: Journal of Medical Case Reports - Category: General Medicine Source Type: research
LITFL • Life in the Fast Lane Medical Blog LITFL • Life in the Fast Lane Medical Blog - Emergency medicine and critical care medical education blog aka Tropical Travel Trouble 009 The diagnosis of HIV is no longer fatal and the term AIDS is becoming less frequent. In many countries, people with HIV are living longer than those with diabetes. This post will hopefully teach the basics of a complex disease and demystify some of the potential diseases you need to consider in those who are severely immunosuppressed. While trying to be comprehensive this post can not be exhaustive (as you can imagine any patient with ...
Source: Life in the Fast Lane - Category: Emergency Medicine Authors: Tags: Clinical Cases Tropical Medicine AIDS art cryptococcoma cryptococcus HIV HIV1 HIV2 PEP PrEP TB toxoplasma tuberculoma Source Type: blogs
Chronic meningitis is a syndrome defined by the presence of clinical signs and symptoms of meningitis or meningoencephalitis with a persisting cerebral spinal fluid (CSF) pleocytosis that are present for at least 4 weeks. The differential diagnosis is broad, with categories including neoplastic, paraneoplastic, autoimmune, and noninfectious inflammatory disorders and central nervous system (CNS) infections. The exact frequency of the different etiologies often varies tremendously across reports; however, among most institutions, common infectious causes of chronic meningitis includeMycobacterium tuberculosis and fungal men...
Source: JAMA Neurology - Category: Neurology Source Type: research
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