Cestode infections in non-human primates suggest the existence of zoonotic cycles in the area surrounding the Strasbourg primatology center

Background: Several cases of infections due to Echinococcus multilocularis, Taenia martis and Taenia crassiceps were recently described in various species of captive non-human primates (NHPs) harbored in the Strasbourg Primate Center (SPC). Furthermore, one of the first cases of human cysticercosis due to T. martis was described in the Strasbourg region. These data suggest the existence of zoonotic cycles of tapeworm infections in the direct environment of the SPC. The aim of our study was to assess the prevalence of larval cestode infections among intermediate and definitive hosts in the close neighborhood of the center. We analyzed carnivore mammal fecal samples as well as rodent carcasses, collected inside or near the SPC, using PCR. Furthermore, we performed serology for Echinococcus spp. and Taenia spp. on NHP sera. Results: We found that 14.5% (95% CI [8.6; 20.4]) of 138 carnivore feces were positive for E. multilocularis-DNA, as well as 25% (95% CI [5.5; 57.2]) of 12 rodent carcasses, and 5.1% (95% CI [1.4; 8.7]) for T. martis or T. crassiceps. Of all NHPs tested, 10.1% (95% CI [3.8; 16.4]) were seropositive for Echinococcus spp. and 8.2% (95% CI [1.3; 15.1]) for Taenia spp. Conclusions: Our data support the existence of zoonotic cycles of larval cestode infections in the direct environment of the primatology center affecting NHPs harbored in the SPC, potentially threatening the human population living in this area. Since this zoonotic risk is borne by local wildlife, and given the severity of these infections, it seems necessary to put in place measures to protect captive NHPs, and further studies to better assess the risk to human populations

Une nouvelle approche de l’immunité innée lors de la toxoplasmose oculaire : le rôle méconnu des interférons de type I et III

Ocular toxoplasmosis (TO) is an inflammatory condition of the eye caused by infection with the protozoan parasite Toxoplasma gondii. The aim of this study was to explore the role of interferon-β (type I) and IFNs-λ (type III) during TO. Using in vitro models of human retinal cultures, we studied the expression of different cytokines, parasitic proliferation and permeability of retinal epithelium cell monolayers (RPEC) in response to stimulation by type I & III IFNs and infection. We show that most of the cells tested are reactive to stimulation by type I and type III IFNs, that infection with T. gondii induces the expression of type I and type III IFNs, that stimulation of RPEC by type I IFNs limits parasitic proliferation during the infection of these cells by T. gondii and that the IFNs-λ prevent the disjunction of the RPEC following infection by T. gondii.La toxoplasmose oculaire (TO) est une affection inflammatoire de l’œil consécutive à l’infection par le parasite protozoaire Toxoplasma gondii. L’objectif de cette étude était d’explorer le rôle de l’interféron-β (type I) et des IFNs-λ (type III) au cours de la TO. À l’aide de modèles in vitro de cultures rétiniennes humaines nous avons étudié l’expression de différentes cytokines, la prolifération parasitaire et la perméabilité de monocouches de cellules d’épithélium rétinien (RPEC) en réponse à la stimulation par des IFNs de type I et III et à l’infection. Nous montrons que la plupart des cellules testées sont réactives à la stimulation par des IFNs de type I et de type III, que l’infection par T. gondii induit l’expression d’IFNs de type I et de type III, que la stimulation de RPEC par des IFNs de type I limite la prolifération parasitaire lors de l’infection de ces cellules par T. gondii et que les IFNs-λ préviennent la disjonction des RPEC consécutive à l’infection par T. gondii

A new approach to innate immunity during ocular toxoplasmosis : the little-known role of type I and III interferons

La toxoplasmose oculaire (TO) est une affection inflammatoire de l’œil consécutive à l’infection par le parasite protozoaire Toxoplasma gondii. L’objectif de cette étude était d’explorer le rôle de l’interféron-β (type I) et des IFNs-λ (type III) au cours de la TO. À l’aide de modèles in vitro de cultures rétiniennes humaines nous avons étudié l’expression de différentes cytokines, la prolifération parasitaire et la perméabilité de monocouches de cellules d’épithélium rétinien (RPEC) en réponse à la stimulation par des IFNs de type I et III et à l’infection. Nous montrons que la plupart des cellules testées sont réactives à la stimulation par des IFNs de type I et de type III, que l’infection par T. gondii induit l’expression d’IFNs de type I et de type III, que la stimulation de RPEC par des IFNs de type I limite la prolifération parasitaire lors de l’infection de ces cellules par T. gondii et que les IFNs-λ préviennent la disjonction des RPEC consécutive à l’infection par T. gondii.Ocular toxoplasmosis (TO) is an inflammatory condition of the eye caused by infection with the protozoan parasite Toxoplasma gondii. The aim of this study was to explore the role of interferon-β (type I) and IFNs-λ (type III) during TO. Using in vitro models of human retinal cultures, we studied the expression of different cytokines, parasitic proliferation and permeability of retinal epithelium cell monolayers (RPEC) in response to stimulation by type I & III IFNs and infection. We show that most of the cells tested are reactive to stimulation by type I and type III IFNs, that infection with T. gondii induces the expression of type I and type III IFNs, that stimulation of RPEC by type I IFNs limits parasitic proliferation during the infection of these cells by T. gondii and that the IFNs-λ prevent the disjunction of the RPEC following infection by T. gondii

Pathophysiology of ocular toxoplasmosis: Facts and open questions.

Infections with the protozoan parasite Toxoplasma gondii are frequent, but one of its main consequences, ocular toxoplasmosis (OT), remains poorly understood. While its clinical description has recently attracted more attention and publications, the underlying pathophysiological mechanisms are only sparsely elucidated, which is partly due to the inherent difficulties to establish relevant animal models. Furthermore, the particularities of the ocular environment explain why the abundant knowledge on systemic toxoplasmosis cannot be just transferred to the ocular situation. However, studies undertaken in mouse models have revealed a central role of interferon gamma (IFNγ) and, more surprisingly, interleukin 17 (IL17), in ocular pathology and parasite control. These studies also show the importance of the genetic background of the infective Toxoplasma strain. Indeed, infections due to exotic strains show a completely different pathophysiology, which translates in a different clinical outcome. These elements should lead to more individualized therapy. Furthermore, the recent advance in understanding the immune response during OT paved the way to new research leads, involving immune pathways poorly studied in this particular setting, such as type I and type III interferons. In any case, deeper knowledge of the mechanisms of this pathology is needed to establish new, more targeted treatment schemes

New Insights into the Pathogenesis of Giant Cell Arteritis: Mechanisms Involved in Maintaining Vascular Inflammation

The giant cell arteritis (GCA) pathophysiology is complex and multifactorial, involving a predisposing genetic background, the role of immune aging and the activation of vascular dendritic cells by an unknown trigger. Once activated, dendritic cells recruit CD4 T cells and induce their activation, proliferation and polarization into Th1 and Th17, which produce interferon-gamma (IFN-γ) and interleukin-17 (IL-17), respectively. IFN-γ triggers the production of chemokines by vascular smooth muscle cells, which leads to the recruitment of additional CD4 and CD8 T cells and also monocytes that differentiate into macrophages. Recent data have shown that IL-17, IFN-γ and GM-CSF induce the differentiation of macrophage subpopulations, which play a role in the destruction of the arterial wall, in neoangiogenesis or intimal hyperplasia. Under the influence of different mediators, mainly endothelin-1 and PDGF, vascular smooth muscle cells migrate to the intima, proliferate and change their phenotype to become myofibroblasts that further proliferate and produce extracellular matrix proteins, increasing the vascular stenosis. In addition, several defects in the immune regulatory mechanisms probably contribute to chronic vascular inflammation in GCA: a defect in the PD-1/PD-L1 pathway, a quantitative and qualitative Treg deficiency, the implication of resident cells, the role of GM-CSF and IL-6, the implication of the NOTCH pathway and the role of mucosal-associated invariant T cells and tissue-resident memory T cells

Intestinal microsporidiosis in Strasbourg from 2014 to 2016: emergence of an Enterocytozoon bieneusi genotype of Asian origin

International audienceMicrosporidia cause opportunistic infections in highly immunodeficient individuals. Few studies on the epidemiology of these infections have been conducted in France. Between 2014 and 2016, we undertook a study to estimate the prevalence and circulating genotypes of this fungus-related microorganism among the population of Strasbourg University Hospital. Samples were collected from hospitalized patients and analyzed using microscopy and molecular assays. Strains from positive subjects were sequenced for genotyping. Only 7/661 patients (1.1%) were positive for microsporidia, and the only species identified was Enterocytozoon bieneusi. Two patients presented immunodeficiency linked to AIDS, and five transplant recipients presented immunodeficiency linked to immunosuppressive therapies. Only five patients received specific antimicrosporidial treatment, but clinical outcomes were good in all cases. We identified four genotypes: A and D in patients with AIDS, and C and S9 in transplant recipients. To date, genotype S9 has been described only once. This genotype is similar to those found in farm animals in China. Because some of these animals have been introduced to Central Europe, we postulate that this genotype might be of Asian origin. Thus, genotyping microsporidial strains may be of epidemiological and clinical interest to identify potential outbreak sources depending on the infecting strains

Mimickers of Large Vessel Giant Cell Arteritis

Giant cell arteritis (GCA) is a large-vessel granulomatous vasculitis occurring in patients over 50-year-old. Diagnosis can be challenging because there is no specific biological test or other diagnoses to consider. Two main phenotypes of GCA are distinguished and can be associated. First, cranial GCA, whose diagnosis is usually confirmed by the evidence of a non-necrotizing granulomatous panarteritis on temporal artery biopsy. Second, large-vessel GCA, whose related symptoms are less specific (fever, asthenia, and weight loss) and for which other diagnoses must be implemented if there is neither cephalic GCA nor associated polymyalgia rheumatica (PMR) features chronic infection (tuberculosis, Coxiella burnetti), IgG4-related disease, Erdheim Chester disease, and other primary vasculitis (Behçet disease, relapsing polychondritis, or VEXAS syndrome). Herein, we propose a review of the main differential diagnoses to be considered regarding large vessel vasculitis