Pathogenesis Of Infection Research Articles

A complex remodeling of cellular homeostasis distinguishes RSV/SARS-CoV-2 co-infected A549-hACE2 expressing cell lines.

Concurrent infections with two or more pathogens with analogous tropism, such as RSV and SARS-CoV-2, may antagonize or facilitate each other, modulating disease outcome. Clinically, discrepancies in the severity of symptoms have been reported in children with RSV/SARS-CoV-2 co-infection. Herein, we propose an in vitro co-infection model to assess how RSV/SARS-CoV-2 co-infection alters cellular homeostasis. To this end, A549-hACE2 expressing cells were either infected with RSV or SARS-CoV-2 alone or co-infected with both viruses. Viral replication was assessed at 72 hours post infection by droplet digital PCR, immunofluorescence, and transmission electron microscopy. Anti-viral/receptor/autophagy gene expression was evaluated by RT-qPCR and confirmed by secretome analyses and intracellular protein production. RSV/SARS-CoV-2 co-infection in A549-hACE2 cells was characterized by: 1) an increase in the replication rate of RSV compared to single infection; 2) an increase in one of the RSV host receptors, ICAM1; 3) an upregulation in the expression/secretion of pro-inflammatory genes; 4) a rise in the number and length of cellular conduits; and 5) augmented autophagosomes formation and/or alteration of the autophagy pathway. These findings suggest that RSV/SARS-CoV-2 co-infection model displays a unique and specific viral and molecular fingerprint and shed light on the viral dynamics during viral infection pathogenesis. This in vitro co-infection model may represent a potential attractive cost-effective approach to mimic both viral dynamics and host cellular responses, providing in future readily measurable targets predictive of co-infection progression.

The Role of the NRF2 Pathway in the Pathogenesis of Viral Respiratory Infections.

In humans, acute and chronic respiratory infections caused by viruses are associated with considerable morbidity and mortality. Respiratory viruses infect airway epithelial cells and induce oxidative stress, yet the exact pathogenesis remains unclear. Oxidative stress activates the transcription factor NRF2, which plays a key role in alleviating redox-induced cellular injury. The transcriptional activation of NRF2 has been reported to affect both viral replication and associated inflammation pathways. There is complex bidirectional crosstalk between virus replication and the NRF2 pathway because virus replication directly or indirectly regulates NRF2 expression, and NRF2 activation can reversely hamper viral replication and viral spread across cells and tissues. In this review, we discuss the complex role of the NRF2 pathway in the regulation of the pathogenesis of the main respiratory viruses, including coronaviruses, influenza viruses, respiratory syncytial virus (RSV), and rhinoviruses. We also summarize the scientific evidence regarding the effects of the known NRF2 agonists that can be utilized to alter the NRF2 pathway.

Mesenchymal stem cell therapy for COVID-19 infection.

COVID-19 emerged in December 2019 in Wuhan, China, spread worldwide rapidly, and caused millions of deaths in a short time. Many preclinical and clinical studies were performed to discover the most efficient therapy to reduce the mortality of COVID-19 patients. Among various approaches for preventing and treating COVID-19, mesenchymal stem cell (MSC) therapy can be regarded as a novel and efficient treatment for managing COVID-19 patients. In this review, we explain the pathogenesis of COVID-19 infection in humans and discuss the role of MSCs in suppressing the inflammation and cytokine storm produced by COVID-19. Then, we reviewed the clinical trial and systematic review studies that investigated the safety and efficacy of MSC therapy in the treatment of COVID-19 infection.

Experimental Seneca Valley virus infection in sows and their offspring

Neonatal mortality has been increasingly reported on swine breeding farms experiencing swine idiopathic vesicular disease (SIVD) outbreaks, which can be accompanied by lethargy, diarrhea, and neurologic signs in neonates. Seneca Valley Virus (SVV), or Senecavirus A, has been detected in clinical samples taken from pigs with SIVD. Experimental SVV inoculation has caused vesicular disease in pigs, particularly during the stages from weaning to finishing. However, it remains crucial to investigate whether SVV directly contributes to the increase in neonatal mortality rates. The following study was conducted to chronicle the pathogenesis of SVV infection in sows and their offspring. Ten sows were intranasally inoculated with 4.75 × 107 plaque-forming units of the virus per sow either late in gestation (n = 5) or within fourteen days of farrowing (n = 5). Each sow replicated SVV following intranasal inoculation, but only one out of ten sows developed a vesicular lesion on the snout. Evidence of transplacental infection was observed in two litters, and an additional two litters became infected following parturition out of five litters from sows inoculated in late gestation. No clinical signs were observed in the infected neonates. Likewise, no clinical signs were observed in the other five litters inoculated after farrowing, although each piglet did replicate the challenge virus. In this study, the experimental challenge of SVV did not result in neonatal mortality in contrast to observations in the field; however, it has shed light on the pathogenesis of the virus, the transmission of SVV between sows and their offspring, and host immune response that can help shape control measures in the field.

Integrated metabolomics and transcriptomics analyses reveal metabolic responses to TGEV infection in porcine intestinal epithelial cells.

Transmissible gastroenteritis virus (TGEV) is a coronavirus that infects piglets with severe diarrhoea, vomiting, dehydration, and even death, causing huge economic losses to the pig industry. The underlying pathogenesis of TGEV infection and the effects of TGEV infection on host metabolites remain poorly understood. To investigate the critical metabolites and regulatory factors during TGEV infection in intestinal porcine epithelial cells (IPEC-J2), we performed metabolomic and transcriptomic analyses of TGEV-infected IPEC-J2 cells by LC/MS and RNA-seq techniques. A total of 87 differential metabolites and 489 differentially expressed genes were detected. A series of metabolites and candidate genes from glutathione metabolism and AMPK signalling pathway were examined through combined analysis of metabolome and transcriptome. We found glutathione peroxidase 3 (GPX3) is markedly reduced after TGEV infection, and a significant negative correlation between AMPK signalling pathway and TGEV infection. Exogenous addition of the AMPK activator COH-SR4 significantly downregulates stearoyl coenzyme A (SCD1) mRNA and inhibits TGEV replication; while exogenous GSK-690693 significantly promotes TGEV infection by inhibiting AMPK signalling pathway. In summary, our study provides insights into the key metabolites and regulators for TGEV infection from the metabolome and transcriptome perspective, which will offer promising antiviral metabolic and molecular targets and enrich the understanding of the existence of a similar mechanism in the host.

A review of the latest research and development of the pathogenesis and treatment of COVID-19

The novel coronavirus is a respiratory transmitted disease caused by the severe acute respiratory syndrome Coronavirus 2 (SARS-Cov-2). The outbreak of the novel coronavirus disease 2019 (COVID-19) began in China at the end of 2019. It is surprisingly highly contagious, and the original virus has a strong fatality rate. Scientists responded quickly to study the structure and genomic characteristics of the virus, gained an in-depth understanding of the infection characteristics and pathogenesis of the virus, and provided valuable experience for the clinical diagnosis and treatment of the novel coronavirus. At present, scientists are actively working on vaccines and treatments to meet the challenges of the novel coronavirus. Although some breakthroughs have been made in vaccine research and development, the global epidemic is still serious. This article summarizes the latest research results in order to provide inspiration for the control, diagnosis, treatment, and prevention of COVID-19 so as to protect people's life and health.

Newcastle disease virus activates the PI3K/AKT signaling pathway by targeting PHLPP2 degradation to delay cell apoptosis and promote viral replication

Newcastle disease (ND) is a highly pathogenic, contagious, and fatal infectious disease in poultry caused by the Newcastle disease virus (NDV). The PI3K/AKT signaling pathway is a phosphorylation cascade that participates in regulating several cellular functions. Viruses reportedly regulate the course of infection through the PI3K/AKT axis. Here, we aimed to analyze the pathogenesis of NDV infection mediated by the PI3K/AKT signaling pathway activation. We found that NDV infection can phosphorylate AKT to activate the PI3K/AKT axis both in vitro and in vivo. Flow cytometry and Caspase-3 activity assay showed that NDV infection could inhibit cell apoptosis. The activation or inhibition of the PI3K/AKT signaling pathway activity significantly inhibited or promoted NDV-mediated apoptosis. Furthermore, inhibition of cell apoptosis significantly promoted NDV replication. Overall, our results showed that NDV infection activates the PI3K/AKT signaling pathway and inhibits cell apoptosis, thus promoting viral replication. In this context, the reduced expression of PHLPP2 protein mediated by NDV infection could be inhibited by MG132. PHLPP2 expression reversely and positively regulated NDV replication and cell apoptosis, respectively. These results indicated that NDV infection-mediated activation of the PI3K/AKT signaling pathway and the inhibition of apoptosis depend on the ubiquitin-proteasome degradation of the PHLPP2 protein. Co-IP and indirect immunofluorescence results showed that NDV V protein could interact with PHLPP2 protein, indicating that NDV targeted PHLPP2 protein degradation through V protein to activate the PI3K/AKT signaling pathway. This study deepens our understanding of the molecular mechanisms of NDV infection, providing a theoretical basis for ND prevention and control.

Long non-coding RNA expression in PBMCs of patients with active pulmonary tuberculosis.

Mycobacterium tuberculosis (Mtb) infection is the primary cause of the chronic infectious illness tuberculosis (TB). Long non-coding RNAs (lncRNAs) are functional RNA molecules that cannot be translated into proteins and play a crucial role in regulating the immune system's innate and adaptive responses. It has been demonstrated that the dysregulation of lncRNA expression is associated with various human diseases. However, the mechanism underlying the involvement of so many lncRNAs in the immune response to TB infection remains unclear. The objective of our current study was to identify a number of significantly differentially expressed lncRNAs in peripheral blood mononuclear cells (PBMCs) from TB patients and to select the most indicative lncRNAs as potential biomarkers for active pulmonary tuberculosis. Microarray analysis was performed to determine the lncRNA and mRNA expression profiles in TB patients using a case-control model. The differentially expressed lncRNAs were subjected to gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis to investigate potential roles and pathways associated with the pathogenesis of TB infection, and to screen lncRNAs specifically linked to TB infection. Using real-time fluorescence quantitative PCR (QRT-PCR), specific lncRNAs were identified in TB patients and latent infections. Our findings revealed that various signaling pathways were differentially expressed in TB-infected individuals, suggesting a potential role for lncRNAs in the immunological responses driven by TB infection. This study provides crucial guidelines for future functional research. Upregulated lncRNAs were mainly enriched in Neutrophil extracellular trap formation and Chemokine signaling pathways, while downregulated lncRNAs were enriched in Neuroactive ligand-receptor interaction and Cushing syndrome in TB PBMCs. Furthermore, we found that lnc-XPNPEP1-5, lnc-CASKIN2-2, lnc-HSPA13-6, lnc-CLIC5-1, and LINC02502 were significantly downregulated in TB-infected patients, while LINC00528, lnc-SLC45A4-3, and LINC00926 were significantly upregulated in TB patients and latent infections. These eight lncRNAs, identified as novel biological marker candidates for diagnosing TB infection, were validated by real-time fluorescence quantitative PCR (QRT-PCR). The abnormally expressed lncRNAs identified in this research may provide crucial information for understanding the pathophysiological characteristics of TB patients and the dysfunction of PBMCs. Our findings reveal potential targets for early TB diagnosis and therapy, as well as offer new insights into the mechanisms underlying TB infection.

Role of glucocorticoids in pneumocystis pneumonia in patients with non-HIV infection/AIDS (HIV/AIDS) and related mechanisms

Pneumocystis pneumonia (PCP) is an opportunistic infection caused by Pneumocystis carinii and is the most common fungal infection in HIV/AIDS patients. With the routine use of antiretroviral therapy (ART), the incidence of PCP infection in HIV/AIDS patients has decreased and the prognosis has improved significantly. On the other hand, the use of chemoradiotherapy and immunotherapy in patients with cancer, post-transplantation and autoimmune diseases are increasing dramatically, which has led to a similar increase in the incidence of PCP in these non-HIV/AIDS patients. There is a global shift in research on PCP from HIV-infected co-infected PCP (HIV-PCP) to non-HIV-infected co-infected PCP. The clinical course of non-HIV-PCP is rapid and severe, and the morbidity and mortality rates are higher than those of HIV-PCP. Studies have shown that 90% of non-HIV-PCP patients have a history of glucocorticoid use prior to infection, such as in patients with hematologic malignancies, solid organ transplants, and rheumatic diseases, and that long-term high-dose glucocorticoid use is an important risk for PCP susceptibility. Clinical practice has shown that PCP often occurs during the tapering of glucocorticoids, and a higher proportion of patients develop diffuse pulmonary lesions and, in more severe cases suffer from life-threatening acute respiratory failure. The pathogenesis of non-HIV infections associated with PCP is not yet clarified, and there is a lack of effective therapeutic practices that require further investigation.

Viral infection and host immune response in diabetes.

Diabetes, a chronic metabolic disorder disrupting blood sugar regulation, has emerged as a prominent silent pandemic. Uncontrolled diabetes predisposes an individual to develop fatal complications like cardiovascular disorders, kidney damage, and neuropathies and aggravates the severity of treatable infections. Escalating cases of Type 1 and Type 2 diabetes correlate with a global upswing in diabetes-linked mortality. As a growing global concern with limited preventive interventions, diabetes necessitates extensive research to mitigate its healthcare burden and assist ailing patients. An altered immune system exacerbated by chronic hyperinflammation heightens the susceptibility of diabetic individuals to microbial infections, including notable viruses like SARS-CoV-2, dengue, and influenza. Given such a scenario, we scrutinized the literature and compiled molecular pathways and signaling cascades related to immune compartments in diabetics that escalate the severity associated with the above-mentioned viral infections in them as compared to healthy individuals. The pathogenesis of these viral infections that trigger diabetes compromises both innate and adaptive immune functions and pre-existing diabetes also leads to heightened disease severity. Lastly, this review succinctly outlines available treatments for diabetics, which may hold promise as preventive or supportive measures to effectively combat these viral infections in the former.

A Mouse Model to Study the Pathogenesis of γ-herpesviral Infections in Germinal Center B Cells.

CD30-positive germinal center (GC)-derived B cell lymphomas are frequently linked to Epstein-Barr Virus (EBV) infection. However, a suitable animal model for the investigation of the interplay between γ-herpesvirus and host cells in B cell pathogenesis is currently lacking. Here, we present a novel in vivo model enabling the analysis of genetically modified viruses in combination with genetically modified GC B cells. As a murine γ-herpesvirus, we used MHV-68 closely mirroring the biology of EBV. Our key finding was that Cre-mediated recombination can be successfully induced by an MHV-68 infection in GC B cells from Cγ1-Cre mice allowing for deletion or activation of loxP-flanked cellular genes. The implementation of PrimeFlow RNA assay for MHV-68 demonstrated the enrichment of MHV-68 in GC and isotype-switched B cells. As illustrations of virus and cellular modifications, we inserted the EBV gene LMP2A into the MHV-68 genome and induced constitutively active CD30-signaling in GC B cells through MHV-68 infections, respectively. While the LMP2A-expressing MHV-68 behaved similarly to wildtype MHV-68, virally induced constitutively active CD30-signaling in GC B cells led to the expansion of a pre-plasmablastic population. The findings underscore the potential of our novel tools to address crucial questions about the interaction between herpesviral infections and deregulated cellular gene-expression in future studies.

Experimental infection of pigs and ferrets with "pre-pandemic," human-adapted, and swine-adapted variants of the H1N1pdm09 Influenza A virus reveals significant differences in viral dynamics and pathological manifestations.

Influenza A viruses are RNA viruses that cause epidemics in humans and are enzootic in the pig population globally. In 2009, pig-to-human transmission of a reassortant H1N1 virus (H1N1pdm09) caused the first influenza pandemic of the 21st century. This study investigated the infection dynamics, pathogenesis, and lesions in pigs and ferrets inoculated with natural isolates of swine-adapted, human-adapted, and "pre-pandemic" H1N1pdm09 viruses. Additionally, the direct-contact and aerosol transmission properties of the three H1N1pdm09 isolates were assessed in ferrets. In pigs, inoculated ferrets, and ferrets infected by direct contact with inoculated ferrets, the pre-pandemic H1N1pdm09 virus induced an intermediary viral load, caused the most severe lesions, and had the highest clinical impact. The swine-adapted H1N1pdm09 virus induced the highest viral load, caused intermediary lesions, and had the least clinical impact in pigs. The human-adapted H1N1pdm09 virus induced the highest viral load, caused the mildest lesions, and had the least clinical impact in ferrets infected by direct contact. The discrepancy between viral load and clinical impact presumably reflects the importance of viral host adaptation. Interestingly, the swine-adapted H1N1pdm09 virus was transmitted by aerosols to two-thirds of the ferrets. Further work is needed to assess the risk of human-to-human aerosol transmission of swine-adapted H1N1pdm09 viruses.

Molecular Mechanisms of Ferroptosis and Its Role in Viral Pathogenesis.

Ferroptosis is a novelty form of regulated cell death, and it is mainly characterized by iron accumulation and lipid peroxidation in the cells. Its underlying mechanism is related to the amino acid, iron, and lipid metabolisms. During viral infection, pathogenic microorganisms have evolved to interfere with ferroptosis, and ferroptosis is often manipulated by viruses to regulate host cell servicing for viral reproduction. Therefore, this review provides a comprehensive overview of the mechanisms underlying ferroptosis, elucidates the intricate signaling pathways involved, and explores the pivotal role of ferroptosis in the pathogenesis of viral infections. By enhancing our understanding of ferroptosis, novel therapeutic strategies can be devised to effectively prevent and treat diseases associated with this process. Furthermore, unraveling the developmental mechanisms through which viral infections exploit ferroptosis will facilitate development of innovative antiviral agents.

A Review on Therapeutic Potential of Indian Herbal Plants to Counter Viral Infection and Disease Pathogenesis

Abstract: Herbal plant extracts or purified phytocomponents have been extensively acknowledged in treating several diseases since time immemorial. The Indian Ayurvedic system and Chinese traditional medicines have documented the medicinal properties of important herbs and their effects. In Ayurveda, polyherbal formulation is known to exhibit better therapeutic efficacy compared to single herb. This review focuses on six key ayurvedic herbal plants namely, Tinosporacordifolia (giloi/guduchi), Withaniasomnifera (Ashwagandha), Glycyrrhiza glabra/Licorice (Mulethi), Zingiberofficinale (Ginger), Emblicaofficinalis(Amla) and Ocimum sanctum (Tulsi).Each of these herbal plants possesses specific phytocomponents that aid them in fighting infections and keeping body healthy and stress free. These medicinal plants are known to exhibit several protective features against various diseases or infections. Here we have particularly emphasized on antioxidant, anti-inflammatory, antimicrobial and immunomodulatory properties which are common in these six plants. Recent literature analysis has revealed Ashwagandha to be protective for Covid-19 too. The formulation from such herbs can exhibit synergism and hence better effectiveness against infection and related diseases. Hence, the importance of these medicinal herbs becomes highly prominent as it maintains the harmonious balance by way of boosting the immunity in a human body. Further, greater mechanistic analyses are required to prove their efficacy to fight infectious diseases like Covid-19. It further opens the arena for in-depth research of identifying and isolating the active components from these herbs and evaluating their potency to inhibit viral infections as polyherbal formulation.

The natural compound Sanggenon C inhibits PRRSV infection by regulating the TRAF2/NF-κB signalling pathway

Porcine reproductive and respiratory syndrome (PRRS) is a serious infectious disease and one of the major causes of death in the global pig industry. PRRS virus (PRRSV) strains have complex and diverse genetic characteristics and cross-protection between strains is low, which complicates vaccine selection; thus, the current vaccination strategy has been greatly compromised. Therefore, it is necessary to identify effective natural compounds for the clinical treatment of PRRS. A small molecule library composed of 720 natural compounds was screened in vitro, and we found that Sanggenon C (SC) was amongst the most effective natural compound inhibitors of PRRSV infection. Compared with ribavirin, SC more significantly inhibited PRRSV infection at both the gene and protein levels and reduced the viral titres and levels of protein expression and inflammatory cytokine secretion to more effectively protect cells from PRRSV infection and damage. Mechanistically, SC inhibits activation of the NF-κB signalling pathway by promoting TRAF2 expression, thereby reducing PRRSV replication. In conclusion, by screening natural compounds, we found that SC suppresses PRRSV infection by regulating the TRAF2/NF-κB signalling pathway. This study contributes to a deeper understanding of the therapeutic targets and pathogenesis of PRRSV infection. More importantly, our results demonstrate that SC has potential as a candidate for the treatment of PRRS.

A Review on Epidemiology, Clinical Manifestation and Diagnostic Approach of Dengue in Bangladesh Perspective

Background: Dengue is an arboviral disease caused by dengue virus; single positive stranded RNA virus of the family Flaviviridae. Symptomatic dengue infection causes a wide range of clinical manifestations; from mild dengue fever (DF) to potentially fatal disease, such as dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS). Dengue is endemic in Bangladesh with recurrent outbreak and is one of the major public health concerns in current period. Therefore; we conducted a literature review to analyze demography, epidemiology, pathogenesis, clinical feature and diagnosis of dengue virus infection. Methods: According to the PRISMA guidelines, the references were selected from PubMed, Web of Science and Google Scholar database using search strings containing a combination of terms that included ”dengue”, “Bangladesh”, “epidemiology”, “outbreak”,” pathogenesis”, “clinical manifestation”, “demography “and “diagnosis”. Quality of references was evaluated by independent contributors. Results: About 167,700 confirmed dengue cases were reported at 16’september’2023 in Bangladesh. Although dengue is endemic in Bangladesh, the current dengue surge is unusual in terms of seasonality and the early sharp increase in comparison to previous years, where the surge started around –late June. Plasma leakages are the main pathophysiological hallmark that distinguishes DHF from DF. Severe plasma leakage can result in hypovolemic shock. Various factors are thought to impact disease presentation and severity. Virus segregation in cell cultures, nucleic acid demonstration by polymerase chain reaction (PCR), and serological detection of viral antigens (such as NS1) or particular antibodies are the preferred microbiological assays for dengue detection. Currently, no specific drugs and licensed vaccines are available to treat dengue disease in any of its clinical presentations for all age group. Conclusion: Understanding the clinical manifestation of dengue infection, prompt diagnosis, appropriate treatment, active and continuous surveillance of cases and vectors are the essential determinants for dengue prevention, control and reducing fatality rate. J Bangladesh Coll Phys Surg 2023; 41: 69-81

Molecular-genetic portrait of virulence of Stenotrophomonas maltophilia

Introduction. Stenotrophomonas maltophilia is an opportunistic pathogen that is intrinsically resistant to a wide range of antibiotics. The bacterium is associated with a number of serious diseases and makes a significant contribution to the pathogenesis of polymicrobial infections. S. maltophilia has a wide range of virulence factors, information about which is currently presented in the form of scattered and unconsolidated data.
 Purposes and objectives: critically analyze and summarize current data regarding the molecular-genetic aspects of S. maltophilia virulence for better understanding of the pathogenesis of infections associated with this pathogen.
 Materials and methods. An analysis of information from 80 modern literary sources devoted to the study of the virulent properties of S. maltophilia at the molecular-genetic level has been carried out. The analysis focuses on the mechanisms of production of virulence factors and their genetic determinants.
 Results.The molecular mechanisms of virulence that determine the infectious process caused by S. maltophilia have been analyzed and summarized, including the adhesive function of the surface structures of the bacterial cell (lipopolysaccharides, pili/fimbriae, flagella), the production of extracellular enzymes, the ability to form biofilms on abiotic surfaces and on the tissues of the macroorganism, the functioning of efflux pumps, secretion of small molecules into the external environment by the intercellular information exchange system Quorum Sensing, as well as the influence of iron metabolism on the virulence properties of S. maltophilia.
 Conclusion. The adaptation mechanisms that allow S. maltophilia to adapt to new habitat niches and survive in the human body and unfavorable environmental conditions have been poorly studied. An analytical review summarizing current information on the molecular-genetic aspects of S. maltophilia virulence will be of interest to clinicians and researchers studying the fundamental mechanisms of virulence.

Neutrophil Extracellular Traps Are Induced by Coronavirus 2019 Disease-Positive Patient Plasma and Persist Longitudinally: A Possible Link to Endothelial Dysfunction as Measured by Syndecan-1.

Background: Neutrophil extracellular trap (NET) formation is a mechanism that neutrophils possess to respond to host infection or inflammation. However, dysregulation of NETosis has been implicated in many disease processes. Although the exact mechanisms of their involvement remain largely unknown, this study aimed to elucidate NET formation over the time course of coronavirus disease 2019 (COVID-19) infection and their possible role in endothelial injury. Patients and Methods: Plasma samples from COVID-19-positive patients were obtained at six timepoints during hospitalization. Neutrophils were extracted from healthy donors and treated with COVID-19-positive patient plasma. Myeloperoxidase (MPO) assay was used to assess for NETosis. Syndecan-1 (SDC-1) enzyme-linked immunosorbent assay (ELISA) was run using the same samples. Immunocytochemistry allowed for further quantification of NETosis byproducts MPO and citrullinated histone 3 (CitH3). The receiver operating characteristic (ROC) curve discriminated between admission levels of SDC-1 and MPO in predicting 30-day mortality and need for ventilator support. Results: Sixty-three patients with COVID-19 were analyzed. Myeloperoxidase was upregulated at day 3, 7, and 14 (p = 0.0087, p = 0.0144, p = 0.0421). Syndecan-1 levels were elevated at day 7 and 14 (p = 0.0188, p = 0.0026). Neutrophils treated with day 3, 7, and 14 plasma expressed increased levels of MPO (p < 0.001). Immunocytochemistry showed neutrophils treated with day 3, 7, and 14 plasma expressed higher levels of MPO (p < 0.001) and higher levels of CitH3 when treated with day 7 and 14 plasma (p < 0.01 and p < 0.05). Admission SDC-1 and MPO levels were found to be independent predictors of 30-day mortality and need for ventilator support. Conclusions: Neutrophil dysregulation can be detrimental to the host. Our study shows that COVID-19 plasma induces substantial amounts of NET formation that persists over the course of the disease. Patients also exhibit increased SDC-1 levels that implicate endothelial injury in the pathogenesis of COVID-19 infection. Furthermore, MPO and SDC-1 plasma levels are predictive of poor outcomes.

Pneumococcus downregulates the molecular weight of the extracellular domain of the epidermal growth factor receptor of alveolar epithelial cells.

Pneumococcus is themajor cause of bacterial and invasive pneumococcal infections. Disrupting the alveolarepithelial barrier is an important step in the pathogenesis of invasivepneumococcal infections. The epidermal growth factor receptor (EGFR) maintainsthe integrity of the alveolar epithelial barrier. In this study, we showed that secretory pneumococcal molecules decrease the molecular weight of EGFR without peptide degradation and inhibit alveolar epithelial cell proliferation via EGFR.

Modeling Paratuberculosis in Laboratory Animals, Cells, or Tissues: A Focus on Their Applications for Pathogenesis, Diagnosis, Vaccines, and Therapy Studies.

Paratuberculosis is a chronic granulomatous enteritis caused by Mycobacterium avium subsp. Paratuberculosis that affects a wide variety of domestic and wild animals. It is considered one of the diseases with the highest economic impact on the ruminant industry. Despite many efforts and intensive research, paratuberculosis control still remains controversial, and the existing diagnostic and immunoprophylactic tools have great limitations. Thus, models play a crucial role in understanding the pathogenesis of infection and disease, and in testing novel vaccine candidates. Ruminant animal models can be restricted by several reasons, related to space requirements, the cost of the animals, and the maintenance of the facilities. Therefore, we review the potential and limitations of the different experimental approaches currently used in paratuberculosis research, focusing on laboratory animals and cell-based models. The aim of this review is to offer a vision of the models that have been used, and what has been achieved or discovered with each one, so that the reader can choose the best model to answer their scientific questions and prove their hypotheses. Also, we bring forward new approaches that we consider worth exploring in the near future.