Helicobacter pylori-Toxoplasma gondii interplay with a possible role of IL-10.

Parasites are known for their modulatory effects on the immune response. The impact of toxoplasmosis on the immune response towards H. pylori is being studied in terms of IL-10 levels. This study included 110 patients suffering from persistent dyspepsia and 50 apparently healthy controls. Stool samples were collected and tested for H. pylori using colloidal gold one step test. Sera were examined for anti-Toxoplasma IgM and IgG using ELISA. IL-10 was also tested in the sera using ELISA. We found that Toxoplasma IgM and IgG tested positive in 1.8 % and 40 % of H. pylori positive patients, respectively. H. pylori-infected patients displayed higher IL-10 levels than the healthy controls (84 versus 0.59 pg/ml, respectively, P < 0.001). Classification of H. pylori positive patients according to Toxoplasma IgG titers yielded three groups: negative (58, 52.7 %), equivocal (8, 7.3 %), and positive (44, 40 %) groups, with the highest IL-10 levels detected in the double positive than the negative and the equivocal group (215 pg/ml versus 43 and 112.5 pg/ml, respectively, P < 0.001). There was strong positive correlation between Toxoplasma IgG titers and IL-10 levels (rs = 0.82, P < 0.001). Toxoplasma enhances IL-10 production in response to H. pylori infection. This could ameliorate the inflammatory response in the gastric mucosa, and subsequently more colonization with the H. pylori is achieved, resulting in persistent infection.

Association between toxoplasmosis and autoimmune rheumatic diseases in Egyptian patients.

PURPOSE: To explore the association between T. gondii and autoimmune rheumatic diseases (ARDs). METHODS: This study involved 82 patients with ARDs: 44 rheumatoid arthritis (RA), 28 systemic lupus erythematosus (SLE), and 10 systemic sclerosis (SSc) and 61 age- and sex-matched controls. Sociodemographic, clinical, and laboratory data were collected, and disease activity was assessed. Exposure to toxoplasmosis risk factors was investigated. Serological tests for anti-Toxoplasma IgM and IgG antibodies were assessed using ELISA. RESULTS: In SLE patients, a significant difference of T. gondii IgM versus controls was detected (P=.03). In RA and SLE patients, T. gondii IgG showed a significant difference versus controls (34 (77.3%) P=.001 and 18 (64.3%) P=.03, respectively). There was no significant difference in SSc versus controls. Fetal congenital anomalies displayed a significant difference in IgM seropositive compared to seronegative patients (P=.04). Cat exposure showed a significant difference between IgM and IgG seropositive versus seronegative patients (12 (80.0%) P=.02 and 34 (59.6) P=.04, respectively). There was no significant difference in seropositive patients regarding history of abortion, neuro-psychiatric manifestations, disease activity parameters (ESR, CRP), or different regimens of medications. CONCLUSION: Toxoplasma IgM seropositivity is associated with SLE patients. T. gondii IgG seropositivity is associated with both RA and SLE patients. However, Toxoplasma seropositivity had no association with SSc patients. An association between fetal congenital anomalies and IgM seropositivity was demonstrated. A linkage between cat exposure as a risk factor and toxoplasmosis was suggested among ARD patiants. Exploration of impact of toxoplasmosis on ARDs is a necessity through randomized controlled trials.

Association between toxoplasmosis and autoimmune rheumatic diseases in Egyptian patients / Asociación entre toxoplasmosis y enfermedades reumáticas autoinmunes en pacientes egipcios

Purpose: To explore the association between T. gondii and autoimmune rheumatic diseases (ARDs). Methods: This study involved 82 patients with ARDs: 44 rheumatoid arthritis (RA), 28 systemic lupus erythematosus (SLE), and 10 systemic sclerosis (SSc) and 61 age- and sex-matched controls. Sociodemographic, clinical, and laboratory data were collected, and disease activity was assessed. Exposure to toxoplasmosis risk factors was investigated. Serological tests for anti-Toxoplasma IgM and IgG antibodies were assessed using ELISA. Results: In SLE patients, a significant difference of T. gondii IgM versus controls was detected (P=.03). In RA and SLE patients, T. gondii IgG showed a significant difference versus controls (34 (77.3%) P=.001 and 18 (64.3%) P=.03, respectively). There was no significant difference in SSc versus controls. Fetal congenital anomalies displayed a significant difference in IgM seropositive compared to seronegative patients (P=.04). Cat exposure showed a significant difference between IgM and IgG seropositive versus seronegative patients (12 (80.0%) P=.02 and 34 (59.6) P=.04, respectively). There was no significant difference in seropositive patients regarding history of abortion, neuro-psychiatric manifestations, disease activity parameters (ESR, CRP), or different regimens of medications. Conclusion: Toxoplasma IgM seropositivity is associated with SLE patients. T. gondii IgG seropositivity is associated with both RA and SLE patients. However, Toxoplasma seropositivity had no association with SSc patients. An association between fetal congenital anomalies and IgM seropositivity was demonstrated. A linkage between cat exposure as a risk factor and toxoplasmosis was suggested among ARD patiants. Exploration of impact of toxoplasmosis on ARDs is a necessity through randomized controlled trials.(AU)

Propósito: Explorar la asociación entre Toxoplasma gondii y enfermedades reumáticas autoinmunes (ERA).Métodos: Este estudio involucró a 82 pacientes con ERA: 44 con artritis reumatoide (AR), 28 con lupus eritematoso sistémico (LES) y 10 con esclerosis sistémica (SSc); y 61 controles emparejados por edad y sexo. Se recopilaron datos sociodemográficos, clínicos y de laboratorio, y se evaluó la actividad de la enfermedad. Se indagó exposición a factores de riesgo de toxoplasmosis. Las pruebas serológicas de anticuerpos IgM e IgG antitoxoplasma se evaluaron mediante ELISA.Resultados: En pacientes con LES se detectó una diferencia significativa de T. gondii IgM vs. controles (p = 0,03). En pacientes con AR y LES, T. gondii IgG mostró una diferencia significativa frente a los controles (34 [77,3%] p = 0,001 y 18 [64,3%] p = 0,03, respectivamente). No hay diferencia significativa en SSc vs. controles. Las anomalías congénitas fetales mostraron una diferencia significativa en los pacientes seropositivos para IgM en comparación con los pacientes seronegativos (p = 0,04). La exposición a los gatos mostró una diferencia significativa entre los pacientes seropositivos para IgM e IgG frente a los seronegativos (12 [80%] p = 0,02 y 34 [59,6] p = 0,04, respectivamente). No hubo diferencias significativas en pacientes seropositivos con respecto a antecedentes de aborto, manifestaciones neuropsiquiátricas, parámetros de actividad de la enfermedad (ESR, CRP) o diferentes regímenes de medicamentos.(AU)

Clinical and Immunological Impacts of Latent Toxoplasmosis on COVID-19 Patients.

Background Parasites are well-known immune-modulators. They inhibit some aspects of the immune system to ensure persistence inside the host for a long time; meanwhile, they stimulate other immune aspects to assure the survival of the host. Wide variations in the severity of coronavirus disease 2019 (COVID-19) among developed and developing countries were reported during the COVID-19 pandemic. Parasitic infections, including Toxoplasma gondii (T. gondii), were claimed to contribute to such variations. Methods To explore a possible relationship between latent toxoplasmosis and COVID-19 severity, our study included 44 blood samples from moderate/severe COVID-19 patients, who were admitted to Mansoura University Hospitals, Egypt, during the pandemic. Patients' sera were screened for Toxoplasma IgG antibodies using ELISA (Roche Diagnostics, Indianapolis, USA), and the gene expression of important immune markers (iNOS, arginase-1, IFN-γ, TNF-α, IL-6, IL-10, and TGF-ß) was checked using real-time quantitative PCR. Clinical and laboratory data were obtained from the patients' medical records. Results Toxoplasma IgG antibodies were detected in 33 (75%) of patients. None of the studied clinical or laboratory parameters showed any significant changes in relation to toxoplasmosis seroprevalence. Further classification of the patients according to COVID-19 severity and Toxoplasma seroprevalence did not reveal any changes related to toxoplasmosis as well. Conclusion Our study indicates that latent toxoplasmosis has no effect on the severity of COVID-19.

Economic growth, foreign investment, tourism, and electricity production as determinants of environmental quality: empirical evidence from GCC region.

Each economic factor generates both positive and negative externalities regarding environmental quality. Owing to this, the current study aims to explore the impacts of various economic variables on the environmental quality of the Gulf Cooperation Council (GCC) region. By sampling the 24 years (1996-2019) financial statistics of six GCC region countries, we investigate the impact of economic growth, foreign investment, trade volume, tourism investment and revenue, and electricity production on CO2 emissions. The empirical analysis is based upon dynamic least square and fully modified ordinary least square model due to the existence of cointegration. Following the results, economic growth, foreign investment, tourism investment, electricity production, and population density have a positive impact, while trade volume and banking development have a negative impact on the volume of CO2 emissions. The results support the pollution haven hypothesis in the GCC region and have many policies for environmental economists regarding the protection of the natural environment in the long run. In parallel to economic growth, the policy officials from the GCC region should focus on environmental sustainability. They should exert more effort for developing sustainable economic growth policies. The current analysis offers new insights regarding the dynamic role of various economic factors in establishing the CO2 emission volume in the GCC region.

ON and OFF Signaling Pathways in the Retina and the Visual System.

Visual processing starts at the retina of the eye, and signals are then transferred primarily to the visual cortex and the tectum. In the retina, multiple neural networks encode different aspects of visual input, such as color and motion. Subsequently, multiple neural streams in parallel convey unique aspects of visual information to cortical and subcortical regions. Bipolar cells, which are the second order neurons of the retina, separate visual signals evoked by light and dark contrasts and encode them to ON and OFF pathways, respectively. The interplay between ON and OFF neural signals is the foundation for visual processing for object contrast which underlies higher order stimulus processing. ON and OFF pathways have been classically thought to signal in a mirror-symmetric manner. However, while these two pathways contribute synergistically to visual perception in some instances, they have pronounced asymmetries suggesting independent operation in other cases. In this review, we summarize the role of the ON-OFF dichotomy in visual signaling, aiming to contribute to the understanding of visual recognition.

Bone Morphogenetic Proteins and Diabetic Retinopathy.

Bone morphogenetic proteins (BMPs) play an important role in bone formation and repair. Recent studies underscored their essential role in the normal development of several organs and vascular homeostasis in health and diseases. Elevated levels of BMPs have been linked to the development of cardiovascular complications of diabetes mellitus. However, their particular role in the pathogenesis of microvascular dysfunction associated with diabetic retinopathy (DR) is still under-investigated. Accumulated evidence from our and others' studies suggests the involvement of BMP signaling in retinal inflammation, hyperpermeability and pathological neovascularization in DR and age-related macular degeneration (AMD). Therefore, targeting BMP signaling in diabetes is proposed as a potential therapeutic strategy to halt the development of microvascular dysfunction in retinal diseases, particularly in DR. The goal of this review article is to discuss the biological functions of BMPs, their underlying mechanisms and their potential role in the pathogenesis of DR in particular.

PDL-1 Blockade Prevents T Cell Exhaustion, Inhibits Autophagy, and Promotes Clearance of Leishmania donovani.

Leishmania donovani is a causative pathogen of potentially fatal visceral leishmaniasis (VL). Therapeutic agents are available; however, their use is limited because of high cost, serious side effects, and development of antimicrobial resistance. Protective immunity against VL depends on CD4+ Th1 cell-mediated immunity. Studies have shown that progression of VL is due to exhaustion of T cells; however, the mechanism involved is not clearly understood. Here, we examined the role of PD1/PDL-1 in the pathogenesis of VL by using a murine model of VL. Our data indicate that L. donovani is able to elicit initial expansion of gamma interferon-producing CD4+ Th1 and CD8+ T cells at day 7 postinfection (p.i.); however, the frequency of those cells and inflammatory response decreased at day 21 p.i., despite persistence of parasites. Persistent infection-induced expansion of interleukin-10+ FOXP3+ Treg and CD4+ and CD8+ T cells expressing PD1. Blocking of PDL-1 signaling in vivo resulted in restoration of protective type 1 responses by both CD4+ and CD8+ T cells, which resulted in a significant decrease in the parasite burden. Mechanistically, PDL-1 blocking inhibited autophagy, a cellular degradation process hijacked by Leishmania to acquire host cell nutrients for their survival. Inhibition of autophagy was marked by decreased lipidation of microtubule-associated protein 1 light chain 3, a marker of autophagosome formation, and P62 accumulation. Together, our findings show for the first time that anti-PDL-1 antibody is an effective therapeutic approach for restoration of effector arms of protective immunity against VL and subsequent parasite clearance.

Defective expression of ATG4D abrogates autophagy and promotes growth in human uterine fibroids.

Uterine fibroids (UF) are the most common pelvic tumors in women of reproductive-age and they usually cause heavy menstrual bleeding, pain and infertility. Autophagy is a collection of processes that enables the cells to digest and recycle their cytoplasmic contents, such as toxic protein aggregates, defunct or disused organelles and invading microorganisms. Dysregulation in autophagy process were described in neoplasms; however, the contribution of autophagy to the pathogenesis of UF remains unknown. In this study, we demonstrate that autophagy is deregulated in human UF as evidenced by significant accumulation of autophagosome in human UF cells compared to normal myometrium cells. Analysis of the autophagy markers revealed an enhanced initiation of the autophagy in UF tissues compared to their adjacent myometrial tissues (MyoF). However, autophagosome maturation and flux was blocked in UF tissues, as marked by accumulation of LC3-B and P62 protein. This block was associated with defective expression of autophagy-related protein 4 (ATG4) in the UF tissues compared to MyoF in ~90% of patient samples. Silencing of ATG4D in normal human myometrial cells resulted in defective autophagy flux, enhanced cell proliferation and increased extracellular matrix production, which phenocopy UF cell line. This study indicates that impairment of autophagy flux secondary to defective expression of ATG4D expression is a new mechanistic aberration that contributes to UF pathogenesis. Targeting autophagy pathway could provide novel medical therapeutic approach for non-surgical treatment of UF.

NK Cell-Mediated Regulation of Protective Memory Responses against Intracellular Ehrlichial Pathogens.

Ehrlichiae are gram-negative obligate intracellular bacteria that cause potentially fatal human monocytic ehrlichiosis. We previously showed that natural killer (NK) cells play a critical role in host defense against Ehrlichia during primary infection. However, the contribution of NK cells to the memory response against Ehrlichia remains elusive. Primary infection of C57BL/6 mice with Ehrlichia muris provides long-term protection against a second challenge with the highly virulent Ixodes ovatus Ehrlichia (IOE), which ordinarily causes fatal disease in naïve mice. Here, we show that the depletion of NK cells in E. muris-primed mice abrogates the protective memory response against IOE. Approximately, 80% of NK cell-depleted E. muris-primed mice succumbed to lethal IOE infection on days 8-10 after IOE infection, similar to naïve mice infected with the same dose of IOE. The lack of a recall response in NK cell-depleted mice correlated with an increased bacterial burden, extensive liver injury, decreased frequency of Ehrlichia-specific IFN-γ-producing memory CD4+ and CD8+ T-cells, and a low titer of Ehrlichia-specific antibodies. Intraperitoneal infection of mice with E. muris resulted in the production of IL-15, IL-12, and IFN-γ as well as an expansion of activated NKG2D+ NK cells. The adoptive transfer of purified E. muris-primed hepatic and splenic NK cells into Rag2-/-Il2rg-/- recipient mice provided protective immunity against challenge with E. muris. Together, these data suggest that E. muris-induced memory-like NK cells, which contribute to the protective, recall response against Ehrlichia.