Pathogenesis Of Infectious Diseases Research Articles

Sex disparities in influenza: A multiscale network analysis

SummarySex differences in the pathogenesis of infectious diseases because of differential immune responses between females and males have been well-documented for multiple pathogens. However, the molecular mechanism underlying the observed sex differences in influenza virus infection remains poorly understood. In this study, we used a network-based approach to characterize the blood transcriptome collected over the course of infection with influenza A virus from female and male ferrets to dissect sex-biased gene expression. We identified significant differences in the temporal dynamics and regulation of immune responses between females and males. Our results elucidate sex-differentiated pathways involved in the unfolded protein response (UPR), lipid metabolism, and inflammatory responses, including a female-biased IRE1/XBP1 activation and male-biased crosstalk between metabolic reprogramming and IL-1 and AP-1 pathways. Overall, our study provides molecular insights into sex differences in transcriptional regulation of immune responses and contributes to a better understanding of sex biases in influenza pathogenesis.

Genetic Predisposition and the Variable Course of Infectious Diseases.

Contact with a pathogen is followed by variable courses of infectious disease, which are only partly explicable by classical risk factors. The susceptibility to infection is variable, as is the course of disease after infection. In this review, we discuss the extent to which this variation is due to genetic factors of the affected individual (the host). Selective review of the literature on host genetics in infectious disease, with special attention to the pathogens SARSCoV- 2, influenza viruses, Mycobacterium tuberculosis, and human immunodeficiency virus (HIV). Genetic variants of the host contribute to the pathogenesis of infectious diseases. For example, in HIV infection, a relatively common variant leading to a loss of function of the HIV co-receptor CCR5 affects the course of the disease, as do variants in genes of the major histocompatibility complex (MHC) region. Rare monogenic variants of the interferon immune response system contribute to severe disease courses in COVID-19 and influenza (type I interferon in these two cases) and in tuberculosis (type II interferon). An estimated 1.8% of life-threatening courses of COVID-19 in men under age 60 are caused by a deficiency of toll-like receptor 7. The scientific understanding of host genetic factors has already been beneficial to the development of effective drugs. In a small number of cases, genetic information has also been used for individual therapeutic decision-making and for the identification of persons at elevated risk. A comprehensive understanding of host genetics can improve the care of patients with infectious diseases. Until the present, the clinical utility of host genetics has been limited to rare cases; in the future, polygenic risk scores summarizing the relevant genetic variants in each patient will enable a wider benefit. To make this possible, multicenter studies are needed that will systematically integrate clinical and genetic data.

The Role of the Parasite Life Cycle in Pathogenesis of Infectious Diseases

<p><strong>Indonesia is a developing country that has various risk factors that can cause parasitic infections to develop. The role of the life cycle of worms and other parasites has been widely studied before. However, there is still little review of its pathogenesis in Indonesia. The purpose of this article is to examine the role of the parasite life cycle in the pathogenesis of infectious diseases. Based on this review, it can be concluded that <em>Diphyllobothrium latum, Taenia solium, Echinococus granulosus, Hymenolepis nana, Dypilidium caninum, Schistosoma japonicum, Fasciolopsis buski, Heterophyes, Echinostoma, Clonorchis sinensis, Fasciola hepatica, Dicrocoemani, Paragon dencarisius, trichiura, Necator americanus, Ancylostoma duodenale, Stongyloides stercoralis, Trichinela spiralis, Angiostrongylus cantonensis, and Wuchereria bancrofti</em> have different life cycles. This difference will have an impact on the different pathogenesis for each infection. Enforcement and treatment also differ based on the underlying pathogenesis.</strong></p><p><strong><em>Keywords</em></strong> – L<em>ife Cycle, Parasite, Patogenesis, Infectious disease</em></p>

Histone acetylome-wide associations in immune cells from individuals with active Mycobacterium tuberculosis infection

Host cell chromatin changes are thought to play an important role in the pathogenesis of infectious diseases. Here we describe a histone acetylome-wide association study (HAWAS) of an infectious disease, on the basis of genome-wide H3K27 acetylation profiling of peripheral blood granulocytes and monocytes from persons with active Mycobacterium tuberculosis (Mtb) infection and healthy controls. We detected >2,000 differentially acetylated loci in either cell type in a Singapore Chinese discovery cohort (n = 46), which were validated in a subsequent multi-ethnic Singapore cohort (n = 29), as well as a longitudinal cohort from South Africa (n = 26), thus demonstrating that HAWAS can be independently corroborated. Acetylation changes were correlated with differential gene expression. Differential acetylation was enriched near potassium channel genes, including KCNJ15, which modulates apoptosis and promotes Mtb clearance in vitro. We performed histone acetylation quantitative trait locus (haQTL) analysis on the dataset and identified 69 candidate causal variants for immune phenotypes among granulocyte haQTLs and 83 among monocyte haQTLs. Our study provides proof-of-principle for HAWAS to infer mechanisms of host response to pathogens.

Pathogenic Impacts of Bacillus cereus Strains on Crassostrea gigas.

Regarding the economic importance of bivalve farming, a great deal of interest has recently been devoted to studying the pathogenesis of infectious diseases of these mollusks to prepare for public health emergencies. Bacillus cereus is one of these pathogens; it is a ubiquitous soil bacterium responsible for many types of gastrointestinal diseases associated with food. This study was conducted to determine the pathogenic effect of B. cereus on Crassostrea gigas. This effect was studied by assessing hemocytes death using flow cytometry analysis. The results showed that only ∼15% of C. gigas were able to survive after B. cereus artificial infection with 108 CFU (colony-forming unit)/oyster. Evenly, the percentage of nonviable hemocytes gradually increased with the concentration of B. cereus, with a peak value of ∼40% after infection. Indeed, findings showed that this strain is harmful to C. gigas.

Metabolic disorders as a factor in pathogenesis of infectious diseases in cattle

Metabolic disorders as a factor in pathogenesis of infectious diseases in cattle

Nivo serumskog hemokina CCL2/MCP-1 kod bolesnika sa odontogenim infektivnim i inflamatornim bolestima mekog tkiva maksilofacijalne regije i medijastinuma

Aim. The paper was aimed at determining the CCL2/MCP-1 level in patients with odontogenic infectious and inflammatory diseases of soft tissues of the maxillofacial area and mediastinum. Methods. The study involved 46 patients with odontogenic infectious and inflammatory diseases of soft tissues of the maxillofacial area and 12 healthy volunteers. The level of patients' plasma CCL2/MCP-1 level was determined using a kit for specific ELISA. Results. The findings of the studies showed a statistically significant increase in the concentration of plasma CCL2/MCP-1 in patients of all study groups. Our study shows a significant increase in plasma CCL2/MCP-1 level in patients with odontogenic phlegmonas, abscesses and mediastinitis, compared to the group of healthy subjects. Conclusion. CCL2/MCP-1 may play an important role in the pathogenesis of odontogenic infectious and inflammatory diseases of soft tissues of the maxillofacial area and mediastinum, which requires a careful follow-up study.

A mini-review on bovine stromal mesenchymal cells sustainability and innovativeness

Animal experiments are conducted to demonstrate proof-of-concept and mechanisms of action, provide safe cell culture methods, carry out tissue engineering, and study infectious disease pathogenesis. Regarding the sustainable principles of the 3Rs, namely, refinement, reduction, and replacement, animal and human biological systems have been used. By definition, the Wharton's jelly (WJ) layer is a connective tissue localized in the middle of the umbilical vessels and amniotic epithelium. In this review, we would like to state that these cells belong to the division of primitive stromal cells. Because the WJ layer is an economical source of cells, the use of this resource would improve areas such as regenerative medicine, biotechnology, and agronomics worldwide in accordance with sustainability.

The role of microbiota in pathogenesis and development of viral infections

Introduction and purpose
 The microbiota plays an important role in human metabolism, immune system, and development of many chronic diseases, cancers, and infectious diseases. The aim of the study is to present the role of gut microbiota in viral infections, including HBV, Herpesviridae, HIV, and SARS-CoV-2. The newest publications from the last 5 years available on the PubMed database were taken into account.
 A brief description of the state of knowledge
 The mechanism by which bacterias have an impact on viral infection is based on a synthesis of specific short-chain fatty acids (SCFAs) and modulation of cytokine release and immune system function by bacterias. Domination of Gardnerella vaginalis and lack of Lactobacillus in the vaginal microbiome increased the risk of HSV-2 infection in women. Inflammation of the genital tract can influence susceptibility to HIV infection, but probiotics via enhancement of the gut barrier integrity, change TH17/Treg ratio, can restore microbiome composition. LPS - component of the structure of Gram-negative bacteria can be a marker of HBV infection. In the airway microbiome of patients with COVID-19 opportunistic microorganisms were identified.
 Conclusions 
 Diet, intake of probiotics, fecal microbiota transplantation (FMT) are interventions that might be efficient methods in prophylaxis and treatment of viral diseases. Further studies are needed to evaluate the mechanism of action of microbiome in pathogenesis of infectious diseases.

Neutrophils-From Bone Marrow to First-Line Defense of the Innate Immune System.

Neutrophils (polymorphonuclear cells; PMNs) form a first line of defense against pathogens and are therefore an important component of the innate immune response. As a result of poorly controlled activation, however, PMNs can also mediate tissue damage in numerous diseases, often by increasing tissue inflammation and injury. According to current knowledge, PMNs are not only part of the pathogenesis of infectious and autoimmune diseases but also of conditions with disturbed tissue homeostasis such as trauma and shock. Scientific advances in the past two decades have changed the role of neutrophils from that of solely immune defense cells to cells that are responsible for the general integrity of the body, even in the absence of pathogens. To better understand PMN function in the human organism, our review outlines the role of PMNs within the innate immune system. This review provides an overview of the migration of PMNs from the vascular compartment to the target tissue as well as their chemotactic processes and illuminates crucial neutrophil immune properties at the site of the lesion. The review is focused on the formation of chemotactic gradients in interaction with the extracellular matrix (ECM) and the influence of the ECM on PMN function. In addition, our review summarizes current knowledge about the phenomenon of bidirectional and reverse PMN migration, neutrophil microtubules, and the microtubule organizing center in PMN migration. As a conclusive feature, we review and discuss new findings about neutrophil behavior in cancer environment and tumor tissue.

Diagnostic value of cortisol identification in biological body fluid in case of infectious diseases (literature review)

Disorders of control mechanisms caused by glucocorticoid hormones of adrenal cortex have a significant role in the pathogenesis of infectious diseases, first of all, due to cortisol, one of the key hormones with anti-inflammatory activity. Currently the conception about the mechanisms of cortisol influence, its functional abilities, connection with immune and nerve cells, involvement in cytokine regulation, features of free-radical oxidation has been extended. There has been identified the dependence of cortisol influence upon the isoform, amount and affinity of its receptors on target cells. The present review describes the study results concerning cortisol level in case of the most often occurring infectious diseases in children acute respiratory and intestinal infections, infectious diseases of the central nervous system. There has been noticed a considerable data variability about cortisol level in normal state and in pathological one, however, the majority of articles have detected its connection with clinical manifestations and outcomes of the diseases. The study of cortisol level in cerebrospinal fluid is of a special interest in case of neuroinfections, specifying its direct connection with the disease severity and aetiology that gives new possibilities to develop effective diagnostic criteria. In general, the literature data specifies the advanced study of disorders of hypothalamus-hypophysial-adrenal gland functioning, receptor apparatus of target cells, as well as interrelations of cortisol with immune system in case of infectious diseases to reveal new criteria for diagnostics, course prediction and disease outcome, therapy correction.

The association between Fc gamma RIIb expression levels and chronic hepatitis B virus infection progression

BackgroundFc gamma receptor IIb (FcγRIIb) is an important inhibitory receptor that plays vital roles in regulating various immune response processes and the pathogenesis of many infectious diseases. The purpose of our research was to evaluate FcγRIIb expression in serum and liver biopsy specimens from hepatitis B virus (HBV)-infected patients and to explore the association of FcγRIIb with chronic HBV infection.MethodsEnzyme-linked immunosorbent assay (ELISA) was adopted to measure the serum FcγRIIb levels in 119 HBV-infected patients and 24 healthy controls. An immunohistochemical method was then employed to identify FcγRIIb expression in biopsy specimens from patients with chronic hepatitis B (CHB). The integrated optical density (IOD) value was measured to represent FcγRIIb expression levels.ResultsSerum FcγRIIb levels were decreased in CHB patients compared to controls (P < 0.001). The FcγRIIb levels in the CHB patient group were remarkably lower than those in the HBV carrier group (P < 0.001). In addition, FcγRIIb levels were negatively associated with AST and ALT (r = −0.3936, P = 0.0063; r = −0.3459, P = 0.0097, respectively). The IOD values of FcγRIIb expression in the moderate and severe CHB groups were significantly lower than those in the control group (P = 0.006 and P < 0.001, respectively). The FcγRIIb level tended to be lower with pathological changes related to hepatitis. Furthermore, correlation analysis revealed that FcγRIIb had negative correlations with AST and ALT (r = −0.688, P = 0.0016; r = −0.686, P = 0.0017, respectively) but a positive association with the platelet count (r = 0.6464, P = 0.0038).ConclusionsFcγRIIb levels are significantly related to chronic HBV infection and the progression of CHB. Changes in FcγRIIb may affect the progression of liver inflammation and fibrosis in CHB patients.

Cytokines in Liver Transplantation.

Cytokines, soluble mediators of the immune system, play a critical role in the pathogenesis of autoimmune, allergic and infectious diseases. They are also implicated in the initiation and development of allograft rejection. During recent years, there have been considerable advances in generating novel anti-cytokine agents with promoted efficacy and safety, which could be administrated for managing dysregulated cytokine secretion; besides, gene therapy for overexpression of immunomodulatory cytokines has shown substantial improvements. Liver transplantation has been established as a life-saving treatment for end-stage hepatic diseases but the growing number of recipients urge for improved post-transplant care including tolerance induction, infection control and resolving immunosuppressant drugs adverse effects. Cytokines with a wide range of proinflammatory and regulatory properties might be considered as potential therapeutic targets for selective suppression or enhancement of the immune responses in recipients. In the present review, we aimed to summarize the positive and negative effects of cytokines on liver allograft in addition to their prognostic and therapeutic values.

Type I Interferon and the Spectrum of Susceptibility to Viral Infection and Autoimmune Disease: A Shared Genomic Signature.

Type I interferons (IFN-I) and their cognate receptor, the IFNAR1/2 heterodimer, are critical components of the innate immune system in humans. They have been widely explored in the context of viral infection and autoimmune disease where they play key roles in protection against infection or shaping disease pathogenesis. A false dichotomy has emerged in the study of IFN-I where interferons are thought of as either beneficial or pathogenic. This ‘good or bad’ viewpoint excludes more nuanced interpretations of IFN-I biology - for example, it is known that IFN-I is associated with the development of systemic lupus erythematosus, yet is also protective in the context of infectious diseases and contributes to resistance to viral infection. Studies have suggested that a shared transcriptomic signature underpins both potential resistance to viral infection and susceptibility to autoimmune disease. This seems to be particularly evident in females, who exhibit increased viral resistance and increased susceptibility to autoimmune disease. The molecular mechanisms behind such a signature and the role of sex in its determination have yet to be precisely defined. From a genomic perspective, several single nucleotide polymorphisms (SNPs) in the IFN-I pathway have been associated with both infectious and autoimmune disease. While overlap between infection and autoimmunity has been described in the incidence of these SNPs, it has been overlooked in work and discussion to date. Here, we discuss the possible contributions of IFN-Is to the pathogenesis of infectious and autoimmune diseases. We comment on genetic associations between common SNPs in IFN-I or their signalling molecules that point towards roles in protection against viral infection and susceptibility to autoimmunity and propose that a shared transcriptomic and genomic immunological signature may underlie resistance to viral infection and susceptibility to autoimmunity in humans. We believe that defining shared transcriptomic and genomic immunological signatures underlying resistance to viral infection and autoimmunity in humans will reveal new therapeutic targets and improved vaccine strategies, particularly in females.

Informal nutrition symposium: leveraging the microbiome (and the metabolome) for poultry production

Knowledge of gut microbiology of poultry has advanced from a limited ability to culture relatively few microbial species, to attempting to understand the complex interactions between the bird and its microbiome. The Informal Nutrition Symposium 2021 was intended to help poultry scientists to make sense of the implications of the vast amounts of information being generated by researchers. This paper represents a compilation of the talks given at the symposium by leading international researchers in this field. The symposium began with an overview of the historical developments in the field of intestinal microbiology and microbiome research in poultry. Next, the systemic effects of the microbiome on health in the context of the interplay between the intestinal microbiota and the immune system were presented. Because the microbiome and the host communicate and influence each other, the novel field of kinomics (the study of protein phosphorylation) as used in the study of the poultry microbiome was discussed. Protein phosphorylation is a rapid response to the complex of signals among the microbiome, intestinal lumen metabolites, and the host. Then, a description of why an understanding of the role of microbial endocrinology in poultry production can lead to new understanding of the mechanisms by which the gut microbiota and the host can interact in defined mechanisms that ultimately determine health, pathogenesis of infectious disease, and behavior was given. Finally, a view forward was presented underscoring the importance of understanding mechanisms in microbiomes in other organ systems and other species. Additionally, the importance of the development of new -omics platforms and data management tools to more completely understand host microbiomes was stressed.

Innovative Instructional Reform and Practice of Oral Microbiology-A Course in Undergraduate Stomatology Curriculum

Oral Microbiology is a vital component of the basic science of stomatology and an important compulsory course for undergraduate students of stomatology, focusing on the oral microbiology and microecology, the pathogenesis of oral infectious diseases, and the relationship between oral microbes and human health. Our faculty team have made reforms of the theory and laboratory teaching of the course Oral Microbiology. We have introduced in the classroom the concept of Three Comprehensive Approaches to Education-the full involvement of everyone, the through-course approach and all-round education-and offered inquiry-based instruction through a combination of extracting the core information from every chapter, using the core information as the foundation, integrating the core information with clinical problems, and using experiment operation to foster in the students an attitude of solving clinical problems through research. These teaching innovations improved the undergraduate students'motivation to learn. We evaluated the teaching effect with questionnaire surveys. The results suggested that the students showed high interest in learning and were satisfied with our teaching innovations. In addition, student performance evaluation for the course showed significant improvement, indicating that the instructional reform program of Oral Microbiology was conducive to students'understanding and mastery of the course content, improved student motivation to learn and their grades, and received positive reviews from the students. We report herein, from three aspects, the course innovations and the experiences gained. We discussed the significance of integrating ideological and political theories teaching in all courses and using innovative teaching materials and teaching models and, highlighted their importance in the education of stomatology students, and proposed suggestions to further improve the course design of Oral Microbiology.

Polymeric micelles and nanomedicines: Shaping the future of next generation therapeutic strategies for infectious diseases

Despite all the advances in understanding the pathogenesis of infectious diseases and the development of novel treatments to combat them, these pathogenic disorders are among the most common reasons for hospitalizations and death worldwide.Polymeric micelles (PMs) are nano-sized drug delivery systems that in the last few years have raised special attention for optimizing the therapy of many infectious diseases, including those considered as neglected by the World Health Organization. These nanoscopic core/shell structures formed by self-assemblies of amphiphilic block copolymers represent an effective delivery system for poorly water-soluble drugs. In the last few years, many micellar formulations were studied for delivery of drugs, genes and nutraceuticals, and some of them are under clinical trials. This review will focus on the applications of polymeric single and mixed micelles for the treatment of infectious diseases and will discuss how these advancements have contributed to improve their pharmacotherapy, with a special emphasis on neglected tropical diseases. A summary of the nanomaterials used for the preparation of PMs is detailed. The current state of the art of several micellar formulations as nanocarriers of FDA-approved drugs for the therapy of many infectious diseases, including those under pre-clinical or clinical trials is provided. Finally, perspectives in the design of a more efficient pharmacotherapy to overcome the multi-drug resistance phenotype of pathogens or host cells are addressed.

Gliotoxicity and Glioprotection: the Dual Role of Glial Cells.

Glial cells (astrocytes, oligodendrocytes and microglia) are critical for the central nervous system (CNS) in both physiological and pathological conditions. With this in mind, several studies have indicated that glial cells play key roles in the development and progression of CNS diseases. In this sense, gliotoxicity can be referred as the cellular, molecular, and neurochemical changes that can mediate toxic effects or ultimately lead to impairment of the ability of glial cells to protect neurons and/or other glial cells. On the other hand, glioprotection is associated with specific responses of glial cells, by which they can protect themselves as well as neurons, resulting in an overall improvement of the CNS functioning. In addition, gliotoxic events, including metabolic stresses, inflammation, excitotoxicity, and oxidative stress, as well as their related mechanisms, are strongly associated with the pathogenesis of neurological, psychiatric and infectious diseases. However, glioprotective molecules can prevent or improve these glial dysfunctions, representing glial cells-targeting therapies. Therefore, this review will provide a brief summary of types and functions of glial cells and point out cellular and molecular mechanisms associated with gliotoxicity and glioprotection, potential glioprotective molecules and their mechanisms, as well as gliotherapy. In summary, we expect to address the relevance of gliotoxicity and glioprotection in the CNS homeostasis and diseases.

Chlamydia evasion of neutrophil host defense results in NLRP3 dependent myeloid-mediated sterile inflammation through the purinergic P2X7 receptor

Chlamydia trachomatis infection causes severe inflammatory disease resulting in blindness and infertility. The pathophysiology of these diseases remains elusive but myeloid cell-associated inflammation has been implicated. Here we show NLRP3 inflammasome activation is essential for driving a macrophage-associated endometritis resulting in infertility by using a female mouse genital tract chlamydial infection model. We find the chlamydial parasitophorous vacuole protein CT135 triggers NLRP3 inflammasome activation via TLR2/MyD88 signaling as a pathogenic strategy to evade neutrophil host defense. Paradoxically, a consequence of CT135 mediated neutrophil killing results in a submucosal macrophage-associated endometritis driven by ATP/P2X7R induced NLRP3 inflammasome activation. Importantly, macrophage-associated immunopathology occurs independent of macrophage infection. We show chlamydial infection of neutrophils and epithelial cells produce elevated levels of extracellular ATP. We propose this source of ATP serves as a DAMP to activate submucosal macrophage NLRP3 inflammasome that drive damaging immunopathology. These findings offer a paradigm of sterile inflammation in infectious disease pathogenesis.

A possible pathogenic correlation between neutrophil elastase (NE) enzyme and inflammation in the pathogenesis of coronavirus disease 2019 (COVID-19)

A growing body of evidence indicates that neutrophil elastase (NE) is involved in the pathogenesis of respiratory infectious diseases, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study aimed to analyze the dynamic changes in serum levels of NE associated with inflammation, disease activity, and mortality rate in patients with COVID-19. We measured the serum concentrations of NE, C-Reactive protein (CRP), interleukin (IL)- 4, IL-6, IL-8, IL-10, and vitamin D levels in 83 ICU and 69 non-ICU patients compared with 82 healthy subjects (HS) in three-time points (T1-T3). Serum levels of NE, IL-6, IL-8, and CRP in ICU and non-ICU patients were significantly higher than HS (P < 0.001) in three-time points. Also, serum levels of NE, IL-6, IL-8, and CRP in ICU patients were significantly higher than in non-ICU patients (P < 0.05). On the day of admission (T1), the levels of NE, CRP, IL-6, IL-8 were gradually decreased from T1 to T3. At the same time, IL-4 and IL-10 were gradually increased from T1 to T2 and then reduced to T3. Further analyses demonstrated that the levels of NE, IL-6, and IL-8 in deceased patients were significantly higher than in recovered patients (P < 0.05). The ROC curve analysis demonstrated that markers, including NE, IL-6, and IL-8, were valuable indicators in evaluating the activity of COVID-19. Overall, our results signify the critical role of NE in the pathogenesis of COVID-19, and also, further support that NE has a potential therapeutic target for the attenuation of COVID-19 severity.