The mannose receptor in macrophage biology

The Mannose receptor (MR) is a type I membrane molecule involved in both haemostasis and pathogen recognition. Its extracellular domains have broad ligand specificities: the cysteine-rich (CR) domain is involved in sulphated sugar binding, the C-type lectin-like domains (CTLDs) are responsible for the detection of sugars terminated in mannose, fucose or N-acetylglucosamine, and the fibronectin-type II (FNII) domain mediates collagen binding. Its recently discovered collagen binding ability raised the question of MR facilitating cellular adhesion which would then influence its function as an endocytic receptor in collagen-rich mammalian tissues. For this purpose, the level of MR-mediated endocytosis, and MR expression was analyzed by using bone-marrow-derived macrophages (BM-MΦ) plated on extracellular matrix (ECM) proteins including fibronectin (not a MR ligand), collagen type I or IV (MR-ligands). The results showed no difference in the level of MR-mediated endocytosis and MR expression at both mRNA and protein levels upon MΦ adhesion to collagen. This suggests that MR interaction with collagen may simply be crucial for tissue remodelling and wound healing, rather than adhesion. MR is also expressed in a soluble form (sMR) which is comprised of the extracellular region of intact cell-associated MR (cMR). Even though its precise role is not yet clear, enhanced sMR production was previously shown to help Pneumocystis carinii to evade M phagocytosis by forming a protective coat around the organism. In this work, the mechanism responsible for the fungi-induced MR-shedding was studied by treating MΦ with fungal particles in the presence and the absence of a wide-range of inhibitors. After treatment in serum-free conditions, the cell lysate and cell culture supernatants were analyzed by western blot, for cMR and sMR expression respectively. It was shown that fungi species other than P. carinii can also trigger sMR production, and that this effect mainly takes place through -glucan recognition. Using bio-active particulate -glucan, it was also demonstrated that MR cleavage upon -glucan recognition requires dectin-1-mediated signalling involving Syk, PI3K, and, partially, Raf-1 and that is mediated by a non-secreted metalloproteinase. Dectin-1-mediated MR-shedding may partially explain the contradictive data on the involvement of cMR in the development of immunity against fungi, as well as other pathogens recognised by dectin-1. The ability of pathogens to evade or activate the immune response may depend on the balance between sMR and cMR expression levels

Prevalence of intestinal parasitosis and immunological status of HIV/AIDS patients on antiretroviral therapy in Nyanya General Hospital Abuja, Nigeria

Intestinal parasites, especially in HIV/AIDS patients, are a leading cause of morbidity and mortality worldwide. The aim of this study was to determine the prevalence of intestinal parasitosis and the immune status of HIV/AIDS patients on ART. Two hundred (200) HIV/AIDS patients were recruited from the ART clinic at Nyanya General Hospital in Abuja, Nigeria, for this cross-sectional institution-based research. To collect detailed demographic data, questionnaires were sent out. The direct wet mount, formol-ether concentration, and adjusted Ziehl-Neelsen staining were used to analyze stool samples. Patients' records were analyzed during this study period to assess their CD4+ T-cell count and viral load status. The findings were compared using a contingency table analysis and the chi-square test. The Mann-Whitney test was used to compare quantitative data sets. P value of 0.05 was described as statistically significant (P≤0.05).The findings of our study were 80 (40 percent) of the patients had intestinal parasitosis, with 11 (13.8 percent) of them having multiple parasitosis. Cryptosporidium parvum had the highest prevalence (16%), Entamoeba histolytica /dispar (13%), Giardia lamblia (7%), and Entamoeba coli (3.5%). Strongyloides stercoralis, Ascaris lumbricoides, and Cystoisospora belli each had a prevalence of 2.5 percent. The findings revealed that diarrhoea was linked to cryptosporidiosis, giardiasis, and cystoisosporiasis. In this study, there was no correlation between intestinal parasitosis and immune system function. In HIV/AIDS patients, prolonged and untreated diarrhoea can be crippling and fatal

Fungal Recognition Enhances Mannose Receptor Shedding Through Dectin-1 Engagement

The mannose receptor (MR) is an endocytic type I membrane molecule with a broad ligand specificity that is involved in both hemostasis and pathogen recognition. Membrane-anchored MRis cleaved by a metalloproteinase into functional soluble MR (sMR) composed of the extracellular domains of intact MR. Although sMR production was initially considered a constitutive process, enhanced MR shedding has been observed in response to the fungal pathogen Pneumocystis carinii. In this work, we have investigated the mechanism mediating enhanced MR shedding in response to fungi. We show that other fungal species, including Candida albicans and Aspergillus fumigatus, together with zymosan, a preparation of the cell wall of Saccharomyces cerevisiae, mimic the effect of P. carinii on sMR production and that this effect takes place mainly through β-glucan recognition. Additionally, we demonstrate that MR cleavage in response to C. albicans and bioactive particulate β-glucan requires expression of dectin-1. Our data, obtained using specific inhibitors, are consistent with the canonical Syk-mediated pathway triggered by dectin-1 being mainly responsible for inducing MR shedding, with Raf-1 being partially involved. As in the case of steady-state conditions, MR shedding in response to C. albicans and β-glucan particles requires metalloprotease activity. The induction of MR shedding by dectin-1 has clear implications for the role of MR in fungal recognition, as sMR was previously shown to retain the ability to bind fungal pathogens and can interact with numerous host molecules, including lysosomal hydrolases. Thus, MR cleavage could also impact on the magnitude of inflammation during fungal infection

Long-term prognosis of patients with heart failure: Follow-up results of journey HF-TR study population

Background: Despite advances in therapeutic management of patients with heart failure, there is still an increasing morbidity and mortality all over the world. In this study, we aimed to present the 3-year follow-up outcomes of patients included in the Journey HF-TR study in 2016 that has evaluated the clinical characteristics and management of patients with acute heart failure admitted to the hospital and present a national registry data. Methods: The study was designed retrospectively between November 2016 and December 2019. Patient data included in the previously published Journey HF-TR study were used. Among 1606 patients, 1484 patients were included due to dropout of 122 patients due to inhospital death and due to exclusion of 173 due to incomplete data. The study included 1311 patients. Age, gender, concomitant chronic conditions, precipitating factors, New York Heart Association, and left ventricular ejection fraction factors were adjusted in the Cox regression analysis. Results: During the 3-year follow-up period, the ratio of hospitalization and mortality was 70.5% and 52.1%, respectively. Common causes of mortality were acute decompensation of heart failure and acute coronary syndrome. Angiotensin receptor blockers, beta-blockers, statin, and sacubitril/valsartan were found to reduce mortality. Hospitalization due to acute decompensated heart failure, acute coronary syndrome, lung diseases, oncological diseases, and cerebrovascular diseases was associated with the increased risk of mortality. Implantation of cardiac devices also reduced the mortality. Conclusions: Despite advances in therapeutic management of patients with heart failure, our study demonstrated that the long-term mortality still is high. Much more efforts are needed to improve the inhospital and long-term survival of patients with chronic heart failure

The mannose receptor in macrophage biology

The Mannose receptor (MR) is a type I membrane molecule involved in both haemostasis and pathogen recognition. Its extracellular domains have broad ligand specificities: the cysteine-rich (CR) domain is involved in sulphated sugar binding, the C-type lectin-like domains (CTLDs) are responsible for the detection of sugars terminated in mannose, fucose or N-acetylglucosamine, and the fibronectin-type II (FNII) domain mediates collagen binding. Its recently discovered collagen binding ability raised the question of MR facilitating cellular adhesion which would then influence its function as an endocytic receptor in collagen-rich mammalian tissues. For this purpose, the level of MR-mediated endocytosis, and MR expression was analyzed by using bone-marrow-derived macrophages (BM-MΦ) plated on extracellular matrix (ECM) proteins including fibronectin (not a MR ligand), collagen type I or IV (MR-ligands). The results showed no difference in the level of MR-mediated endocytosis and MR expression at both mRNA and protein levels upon MΦ adhesion to collagen. This suggests that MR interaction with collagen may simply be crucial for tissue remodelling and wound healing, rather than adhesion. MR is also expressed in a soluble form (sMR) which is comprised of the extracellular region of intact cell-associated MR (cMR). Even though its precise role is not yet clear, enhanced sMR production was previously shown to help Pneumocystis carinii to evade M phagocytosis by forming a protective coat around the organism. In this work, the mechanism responsible for the fungi-induced MR-shedding was studied by treating MΦ with fungal particles in the presence and the absence of a wide-range of inhibitors. After treatment in serum-free conditions, the cell lysate and cell culture supernatants were analyzed by western blot, for cMR and sMR expression respectively. It was shown that fungi species other than P. carinii can also trigger sMR production, and that this effect mainly takes place through -glucan recognition. Using bio-active particulate -glucan, it was also demonstrated that MR cleavage upon -glucan recognition requires dectin-1-mediated signalling involving Syk, PI3K, and, partially, Raf-1 and that is mediated by a non-secreted metalloproteinase. Dectin-1-mediated MR-shedding may partially explain the contradictive data on the involvement of cMR in the development of immunity against fungi, as well as other pathogens recognised by dectin-1. The ability of pathogens to evade or activate the immune response may depend on the balance between sMR and cMR expression levels.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Modeling of Breast and Gynecological Cancers Data and Investigating New Biological Findings

The breast and gynecological cancers are two most common fatal cancers’ types in women in the world [1]. In oncological literature, these two cancers types are typically worked together since they are the risk factors of each other if the patient has one of these diseases [2]. In general, the cancers, like the heart diseases, are the systems’ ilnesses in the sense that any malfunctions in the associated transaction pathways cause problems in the activation flow, resulting in tumors. Therefore, the mathematical representation of these complex structures enables us to better understand the actual biological process and to produce the target drug. Accordingly, in this study, we evaluate 10 different publically available datasets which are collected from the GEO database. Originally these data are the gene expression datasets where some of them also have certain descriptive information about the samples. Hereby, from each dataset, we initially generate subnetworks by selecting the most significantly expressed genes and normalize them via the RMA method [3] if they are the Affymetrix data or normalize them via deterministic background and quantile normalizations. Then, we present them via distinct mathematical models such as MARS [4] and CGGM [5] in order to describe the steady-state behaviour of the proteomic activations. Here, we evaluate the performance of every model via the accuracy of the estimates and the computational demand. Later, we also combine these models with the risk factors of each cancer and re-construct more comprehensive mathematical models. Finally, we validate our estimated systems via the associated literature and biologically discuss our new findings. By this way, we can also combine the knowledge of both cancers types under a single and more comprehensive mathematical model. We consider that our mathematical representation can open new avenue about these diseases and help us to ask biologically more interesting question

Helminthotherapy

Helminthotherapy is the stimulation of the host immune system using certain helminths, especially nematodes, to aid in the treatment of inflammatory and autoimmune diseases. The relationship between the development status of countries and the assocaited health profile is extremely complex. The prevalence of autoimmune diseases is extremely low in underdeveloped countries where helminth infections are common. On the other hand, in developed countries, the frequency of autoimmune and chronic inflammatory diseases has increased significantly in the last century. The rise in hygiene standards causing reduction in helmintic infections, is thought to play a role in the increased incidences of inflammatory diseases. This observation has led to “hygiene” and “old friend” hypotheses claiming that some organisms in abundant amounts in the human microenvironment are necessary for the development of a healthy immune system and are associated with immunomodulatory or immune-repressive effects. According to these hypotheses, a decrease in exposure to certain organisms, especially parasites, has caused an increase in immune-mediated diseases. Helminths use a range of immunomodulatory mechanisms that affect the host immune responses, in all aspects, to maintain their persistence within the host. Helminth can skew immune response from TH1 to TH2 phenotype, increase both T- and B-regulatory cell levels, and decrease inflammatory cytokines release. This broad-spectrum modulation of the host immune system has both intended and undesirable consequences. Thanks to this modulation, the host benefits from the suppression of allergic, autoimmune and inflammatory reactions as well as suppression of parasitic damage. The suppressive and regulatory effects of helminths on both acquired and innate immune systems have led to many investigations on their use for treatment purposes. In addition to studies showing the effects of anti-helminthic treatment in enhancing atopic manifestations and inflammatory diseases, helminths have also been shown to have protective effects in animal models of allergy and autoimmune disease. Many studies following this data obtained from animal studies still continue today to both identify helminthic immunomodulatory molecules and to test implementability of helmintotherapy for human diseases

Assessment of Respiratory Viral Co-infections Among SARS-CoV-2-Infected Patients

Introduction: Emerging evidence suggests that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients are at an increased risk for co-infections. The aim of this study was to assess the prevalence of respiratory viral co-infections among SARS-CoV-2 patients via molecular testing. Materials and Methods: Nasopharyngeal swabs of 68 SARS-CoV-2 positive cases detected between December 1, 2020 and December 20, 2021 were subjected to nucleic acid isolation and screening using molecular techniques. Real-time-qPCR analysis was performed using the FTD Respiratory Pathogens 21 Panel Kit. Positive results were further confirmed by QIAstat-Dx™ Respiratory Panel. Results: Co-infections were detected in 7.4% (n= 5/68) of SARS-CoV-2-infected patients. Commonly observed co-infecting pathogens were rhinovirus, parainfluenza virus 4, influenza A H3N2, bocavirus, respiratory syncytial virus, and adenovirus. Overall, co-infections were observed in the ≤35 age group. Patients with co-infections did not require hospitalization. Conclusion: Simultaneous identification of respiratory co-infections in SARS-CoV-2 positive patients offers the possibility of implementing optimized treatment regimens preventing morbidity and mortality