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1.
Immunol Rev ; 303(1): 83-102, 2021 09.
Article in English | MEDLINE | ID: covidwho-1816563

ABSTRACT

Most antibodies produced in the body are of the IgA class. The dominant cell population producing them are plasma cells within the lamina propria of the gastrointestinal tract, but many IgA-producing cells are also found in the airways, within mammary tissues, the urogenital tract and inside the bone marrow. Most IgA antibodies are transported into the lumen by epithelial cells as part of the mucosal secretions, but they are also present in serum and other body fluids. A large part of the commensal microbiota in the gut is covered with IgA antibodies, and it has been demonstrated that this plays a role in maintaining a healthy balance between the host and the bacteria. However, IgA antibodies also play important roles in neutralizing pathogens in the gastrointestinal tract and the upper airways. The distinction between the two roles of IgA - protective and balance-maintaining - not only has implications on function but also on how the production is regulated. Here, we discuss these issues with a special focus on gut and airways.


Subject(s)
Friends , Immunoglobulin A , Humans , Immunity, Mucosal , Intestinal Mucosa , Mucous Membrane , Plasma Cells
2.
Nat Rev Immunol ; 22(3): 144-145, 2022 03.
Article in English | MEDLINE | ID: covidwho-1783993
3.
Nat Rev Gastroenterol Hepatol ; 19(4): 216, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1783990
4.
Mol Med Rep ; 25(4)2022 04.
Article in English | MEDLINE | ID: covidwho-1753714

ABSTRACT

Aberrant TGF­ß/Smad7 signaling has been reported to be an important mechanism underlying the pathogenesis of ulcerative colitis. Therefore, the present study aimed to investigate the effects of a number of potential anti­colitis agents on intestinal epithelial permeability and the TGF­ß/Smad7 signaling pathway in an experimental model of colitis. A mouse model of colitis was first established before anti­TNF­α and 5­aminosalicyclic acid (5­ASA) were administered intraperitoneally and orally, respectively. Myeloperoxidase (MPO) activity, histological index (HI) of the colon and the disease activity index (DAI) scores were then detected in each mouse. Transmission electron microscopy (TEM), immunohistochemical and functional tests, including Evans blue (EB) and FITC­dextran (FD­4) staining, were used to evaluate intestinal mucosal permeability. The expression of epithelial phenotype markers E­cadherin, occludin, zona occludens (ZO­1), TGF­ß and Smad7 were measured. In addition, epithelial myosin light chain kinase (MLCK) expression and activity were measured. Anti­TNF­α and 5­ASA treatments was both found to effectively reduce the DAI score and HI, whilst decreasing colonic MPO activity, plasma levels of FD­4 and EB permeation of the intestine. Furthermore, anti­TNF­α and 5­ASA treatments decreased MLCK expression and activity, reduced the expression of Smad7 in the small intestine epithelium, but increased the expression of TGF­ß. In mice with colitis, TEM revealed partial epithelial injury in the ileum, where the number of intercellular tight junctions and the expression levels of E­cadherin, ZO­1 and occludin were decreased, all of which were alleviated by anti­TNF­α and 5­ASA treatment. In conclusion, anti­TNF­α and 5­ASA both exerted protective effects on intestinal epithelial permeability in an experimental mouse model of colitis. The underlying mechanism may be mediated at least in part by the increase in TGF­ß expression and/or the reduction in Smad7 expression, which can inhibit epithelial MLCK activity and in turn reduce mucosal permeability during the pathogenesis of ulcerative colitis.


Subject(s)
Colitis, Ulcerative/metabolism , Smad7 Protein/genetics , Smad7 Protein/metabolism , Transforming Growth Factor beta/genetics , Transforming Growth Factor beta/metabolism , Animals , Cadherins/metabolism , Colitis, Ulcerative/chemically induced , Colon/pathology , Dextran Sulfate/toxicity , Disease Models, Animal , Female , Intestinal Mucosa/drug effects , Intestinal Mucosa/pathology , Intestinal Mucosa/ultrastructure , Male , Mesalamine/administration & dosage , Mice, Inbred C57BL , Myosin-Light-Chain Kinase/metabolism , Occludin/metabolism , Peroxidase/drug effects , Severity of Illness Index , Signal Transduction/drug effects , Tight Junctions/metabolism , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Zonula Occludens-1 Protein/metabolism
5.
Int J Mol Sci ; 23(6)2022 Mar 10.
Article in English | MEDLINE | ID: covidwho-1742487

ABSTRACT

The published literature makes a very strong case that a wide range of disease morbidity associates with and may in part be due to epithelial barrier leak. An equally large body of published literature substantiates that a diverse group of micronutrients can reduce barrier leak across a wide array of epithelial tissue types, stemming from both cell culture as well as animal and human tissue models. Conversely, micronutrient deficiencies can exacerbate both barrier leak and morbidity. Focusing on zinc, Vitamin A and Vitamin D, this review shows that at concentrations above RDA levels but well below toxicity limits, these micronutrients can induce cell- and tissue-specific molecular-level changes in tight junctional complexes (and by other mechanisms) that reduce barrier leak. An opportunity now exists in critical care-but also medical prophylactic and therapeutic care in general-to consider implementation of select micronutrients at elevated dosages as adjuvant therapeutics in a variety of disease management. This consideration is particularly pointed amidst the COVID-19 pandemic.


Subject(s)
Inflammatory Bowel Diseases/metabolism , Intestinal Mucosa/metabolism , Micronutrients/metabolism , Vitamin A/metabolism , Vitamin D/metabolism , Zinc/metabolism , Animals , COVID-19/epidemiology , COVID-19/metabolism , COVID-19/virology , Humans , Micronutrients/pharmacology , Pandemics/prevention & control , SARS-CoV-2/physiology , Tight Junctions/drug effects , Tight Junctions/metabolism , Vitamin A/pharmacology , Vitamin D/pharmacology , Vitamins/metabolism , Vitamins/pharmacology , Zinc/pharmacology
6.
Front Immunol ; 13: 837443, 2022.
Article in English | MEDLINE | ID: covidwho-1742219

ABSTRACT

An ideal protective vaccine against SARS-CoV-2 should not only be effective in preventing disease, but also in preventing virus transmission. It should also be well accepted by the population and have a simple logistic chain. To fulfill these criteria, we developed a thermostable, orally administered vaccine that can induce a robust mucosal neutralizing immune response. We used our platform based on retrovirus-derived enveloped virus-like particles (eVLPs) harnessed with variable surface proteins (VSPs) from the intestinal parasite Giardia lamblia, affording them resistance to degradation and the triggering of robust mucosal cellular and antibody immune responses after oral administration. We made eVLPs expressing various forms of the SARS-CoV-2 Spike protein (S), with or without membrane protein (M) expression. We found that prime-boost administration of VSP-decorated eVLPs expressing a pre-fusion stabilized form of S and M triggers robust mucosal responses against SARS-CoV-2 in mice and hamsters, which translate into complete protection from a viral challenge. Moreover, they dramatically boosted the IgA mucosal response of intramuscularly injected vaccines. We conclude that our thermostable orally administered eVLP vaccine could be a valuable addition to the current arsenal against SARS-CoV-2, in a stand-alone prime-boost vaccination strategy or as a boost for existing vaccines.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/immunology , Coronavirus M Proteins/immunology , Giardia lamblia/immunology , Intestinal Mucosa/immunology , SARS-CoV-2/physiology , Spike Glycoprotein, Coronavirus/immunology , Animals , Antigens, Protozoan/immunology , Cricetinae , Humans , Immunity , Immunization, Secondary , Immunoglobulin A/metabolism , Male , Mice , Mice, Inbred BALB C , Temperature , Vaccine Potency , Vaccines, Virus-Like Particle
7.
Front Immunol ; 13: 838328, 2022.
Article in English | MEDLINE | ID: covidwho-1731785

ABSTRACT

Confirmed SARS-coronavirus-2 infection with gastrointestinal symptoms and changes in microbiota associated with coronavirus disease 2019 (COVID-19) severity have been previously reported, but the disease impact on the architecture and cellularity of ileal Peyer's patches (PP) remains unknown. Here we analysed post-mortem tissues from throughout the gastrointestinal (GI) tract of patients who died with COVID-19. When virus was detected by PCR in the GI tract, immunohistochemistry identified virus in epithelium and lamina propria macrophages, but not in lymphoid tissues. Immunohistochemistry and imaging mass cytometry (IMC) analysis of ileal PP revealed depletion of germinal centres (GC), disruption of B cell/T cell zonation and decreased potential B and T cell interaction and lower nuclear density in COVID-19 patients. This occurred independent of the local viral levels. The changes in PP demonstrate that the ability to mount an intestinal immune response is compromised in severe COVID-19, which could contribute to observed dysbiosis.


Subject(s)
Atrophy/immunology , COVID-19/immunology , Germinal Center/immunology , Intestinal Mucosa/immunology , Peyer's Patches/immunology , B-Lymphocytes/immunology , Humans , Lymphoid Tissue/immunology , Macrophages/immunology , SARS-CoV-2/immunology , T-Lymphocytes/immunology
8.
Cytokine ; 152: 155826, 2022 04.
Article in English | MEDLINE | ID: covidwho-1693705

ABSTRACT

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the causative agent of the newly emerging lung disease pandemic COVID-19. This viral infection causes a series of respiratory disorders, and although this virus mainly infects respiratory cells, the small intestine can also be an important site of entry or interaction, as enterocytes highly express in angiotensin-2 converting enzyme (ACE) receptors. There are countless reports pointing to the importance of interferons (IFNs) with regard to the mediation of the immune system in viral infection by SARS-CoV-2. Thus, this review will focus on the main cells that make up the large intestine, their specific immunology, as well as the function of IFNs in the intestinal mucosa after the invasion of coronavirus-2.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , COVID-19/metabolism , Intestinal Mucosa/metabolism , Intestine, Large/metabolism , SARS-CoV-2/metabolism , COVID-19/pathology , Humans , Intestinal Mucosa/injuries , Intestinal Mucosa/pathology , Intestinal Mucosa/virology , Intestine, Large/injuries , Intestine, Large/pathology , Intestine, Large/virology
9.
Front Cell Infect Microbiol ; 12: 832672, 2022.
Article in English | MEDLINE | ID: covidwho-1686456

ABSTRACT

The gastrointestinal tract (GIT) is considered the largest immunological organ, with a diverse gut microbiota, that contributes to combatting pathogens and maintaining human health. Under physiological conditions, the crosstalk between gut microbiota and intestinal epithelial cells (IECs) plays a crucial role in GIT homeostasis. Gut microbiota and derived metabolites can compromise gut barrier integrity by activating some signaling pathways in IECs. Conversely, IECs can separate the gut microbiota from the host immune cells to avoid an excessive immune response and regulate the composition of the gut microbiota by providing an alternative energy source and releasing some molecules, such as hormones and mucus. Infections by various pathogens, such as bacteria, viruses, and parasites, can disturb the diversity of the gut microbiota and influence the structure and metabolism of IECs. However, the interaction between gut microbiota and IECs during infection is still not clear. In this review, we will focus on the existing evidence to elucidate the crosstalk between gut microbiota and IECs during infection and discuss some potential therapeutic methods, including probiotics, fecal microbiota transplantation (FMT), and dietary fiber. Understanding the role of crosstalk during infection may help us to establish novel strategies for prevention and treatment in patients with infectious diseases, such as C. difficile infection, HIV, and COVID-19.


Subject(s)
COVID-19 , Clostridioides difficile , Gastrointestinal Microbiome , Epithelial Cells , Fecal Microbiota Transplantation , Humans , Intestinal Mucosa , SARS-CoV-2
10.
Front Immunol ; 12: 674074, 2021.
Article in English | MEDLINE | ID: covidwho-1551497

ABSTRACT

As a new infectious disease, COVID-19 is spread through the respiratory tract in most cases. Its source and pathological mechanism are not clear. The most common clinical feature is pulmonary infection. Also, a lot patients have gastrointestinal symptoms. Angiotensin-converting enzyme 2 (ACE2) is a functional cellular receptor for SARS-CoV-2, which is like SARS-CoV, a coronavirus associated with severe acute respiratory syndrome (SARS) outbreak in 2003. The tissues and cells expressing ACE2 are potential targets for SARS-CoV-2 infection, and the high expression of ACE2 in intestinal epithelial cells marks that SARS-CoV-2 may directly infect intestinal epithelial cells. Recent studies also suggest that SARS-CoV-2 existed and replicated in intestinal environment for a long time. The interaction between SARS-CoV-2 and RAS system leads to the decrease of local anti-inflammatory ability. The virus cycle leads to excessive imbalance of immune response and cytokine release. The downregulation of ACE2 after viral infection leads to gastrointestinal dysfunction. The above are the causes of gastrointestinal symptoms. Here, we reviewed the possible causes and mechanisms of gastrointestinal symptoms caused by COVID-19. Additionally, we discussed the influence of gastrointestinal symptoms on the prognosis of patients.


Subject(s)
COVID-19/virology , Intestinal Mucosa/virology , SARS-CoV-2/pathogenicity , Humans
11.
Inflamm Bowel Dis ; 27(Supplement_2): S25-S32, 2021 Nov 15.
Article in English | MEDLINE | ID: covidwho-1522203

ABSTRACT

BACKGROUND: Patients with Crohn's disease (CD) undergo frequent endoscopic procedures, with visualization of the gastrointestinal mucosa central to treatment decision-making. Subsequently, a noninvasive alternative to optical colonoscopy (OC) would be welcomed. One such technology is capsule endoscopy, including the PillCam COLON 2 (PCC2), though research validating its use in ileocolonic CD is limited. This study aims to compare PCC2 with ileocolonoscopy (OC) in assessing mucosal CD through use of a standardized scoring system. METHODS: At an Australian tertiary hospital, same-day PCC2 and ileocolonoscopy results of 47 CD patients, with known nonstricturing disease, were prospectively collected and analyzed for correlation and agreement. Deidentified recordings were reported by a single expert gastroenterologist. Mucosal disease was quantified using the Simple Endoscopic Score for Crohn's Disease (SES-CD). The SES-CD results of paired endoscopic modalities were compared in total per bowel segment and per SES-CD variable. RESULTS: Of 47 PCC2 recordings, 68% were complete, fully assessing terminal ileum to rectum, and OC was complete in 89%. Correlation (r) between total SES-CD scores was strongest in the terminal ileum (r = 0.77, P < .001), with the SES-CD variable of "ulcer detection" showing the strongest agreement. The PCC2 (vs OC) identified additional ulcers in the terminal ileum; ascending, transverse, and descending colon; and rectum; scores were 5 (1), 5 (3), 1 (1), 2 (1), and 2 (2), respectively. CONCLUSIONS: The PCC2 shows promise in assessing ileocolonic mucosa, especially in proximal bowel segments, with greater reach of visualization in the small bowel. Given the resource and safety considerations raised by the Coronavirus disease 2019 pandemic, capsule endoscopy has particular significance.This article aims to contribute to the limited body of research surrounding the validity of capsule endoscopy technology in assessing ileocolonic mucosa in Crohn's Disease patients. In doing so, an alternative option for patients enduring frequent endoscopies is given potential.


Subject(s)
Capsule Endoscopy/methods , Colon/diagnostic imaging , Colonoscopy/methods , Crohn Disease/diagnostic imaging , Intestinal Mucosa/diagnostic imaging , Ulcer/diagnostic imaging , Wound Healing , Australia , COVID-19 , Capsule Endoscopes , Colon/drug effects , Humans , Immunosuppressive Agents/therapeutic use , Intestinal Mucosa/drug effects , SARS-CoV-2 , Severity of Illness Index , Treatment Outcome , Ulcer/drug therapy , Wound Healing/drug effects , Wound Healing/physiology
12.
Nat Commun ; 12(1): 6610, 2021 11 16.
Article in English | MEDLINE | ID: covidwho-1521737

ABSTRACT

COVID-19 typically manifests as a respiratory illness, but several clinical reports have described gastrointestinal symptoms. This is particularly true in children in whom gastrointestinal symptoms are frequent and viral shedding outlasts viral clearance from the respiratory system. These observations raise the question of whether the virus can replicate within the stomach. Here we generate gastric organoids from fetal, pediatric, and adult biopsies as in vitro models of SARS-CoV-2 infection. To facilitate infection, we induce reverse polarity in the gastric organoids. We find that the pediatric and late fetal gastric organoids are susceptible to infection with SARS-CoV-2, while viral replication is significantly lower in undifferentiated organoids of early fetal and adult origin. We demonstrate that adult gastric organoids are more susceptible to infection following differentiation. We perform transcriptomic analysis to reveal a moderate innate antiviral response and a lack of differentially expressed genes belonging to the interferon family. Collectively, we show that the virus can efficiently infect the gastric epithelium, suggesting that the stomach might have an active role in fecal-oral SARS-CoV-2 transmission.


Subject(s)
COVID-19/pathology , Intestinal Mucosa/virology , Organoids/virology , SARS-CoV-2/physiology , Stomach/virology , Virus Replication/physiology , Aborted Fetus , Aged , Animals , COVID-19/virology , Cell Line , Child , Child, Preschool , Chlorocebus aethiops , Humans , Infant , Intestinal Mucosa/pathology , Middle Aged , Organoids/pathology , SARS-CoV-2/isolation & purification , Stomach/pathology
13.
Int J Mol Sci ; 22(21)2021 Oct 21.
Article in English | MEDLINE | ID: covidwho-1480797

ABSTRACT

The intestinal barrier plays an extremely important role in maintaining the immune homeostasis of the gut and the entire body. It is made up of an intricate system of cells, mucus and intestinal microbiota. A complex system of proteins allows the selective permeability of elements that are safe and necessary for the proper nutrition of the body. Disturbances in the tightness of this barrier result in the penetration of toxins and other harmful antigens into the system. Such events lead to various digestive tract dysfunctions, systemic infections, food intolerances and autoimmune diseases. Pathogenic and probiotic bacteria, and the compounds they secrete, undoubtedly affect the properties of the intestinal barrier. The discovery of zonulin, a protein with tight junction regulatory activity in the epithelia, sheds new light on the understanding of the role of the gut barrier in promoting health, as well as the formation of diseases. Coincidentally, there is an increasing number of reports on treatment methods that target gut microbiota, which suggests that the prevention of gut-barrier defects may be a viable approach for improving the condition of COVID-19 patients. Various bacteria-intestinal barrier interactions are the subject of this review, aiming to show the current state of knowledge on this topic and its potential therapeutic applications.


Subject(s)
Bacterial Infections/therapy , Haptoglobins/metabolism , Intestinal Mucosa/metabolism , Probiotics/therapeutic use , Protein Precursors/metabolism , Anti-Bacterial Agents/therapeutic use , Bacterial Infections/drug therapy , Bacterial Infections/pathology , Bacterial Physiological Phenomena , Gastrointestinal Microbiome , Humans , Intestinal Mucosa/microbiology , Mucus/metabolism , Tight Junctions/metabolism
14.
Sci Rep ; 10(1): 5189, 2020 03 23.
Article in English | MEDLINE | ID: covidwho-1454803

ABSTRACT

Stapled hemorrhoidopexy has a few advantages such as less postoperative pain and faster recovery compared with conventional hemorrhoidectomy. There are two major devices used for stapled hemorrhoidopexy, PPH stapler (Ethicon EndoSurgery) and DST stapler (Covidien). This study was conducted to investigate the postoperative outcomes among patients with grade III and IV hemorrhoids who underwent hemorrhoidopexy with either of these two devices. A total of 242 consecutive patients underwent stapled hemorrhoidopexy with either PPH stapler (110 patients) or DST stapler (132 patients) at a single center in 2017. We performed a retrospective case-control study to compare the short-term postoperative outcomes and the complications between these two groups. After matching the cases in terms of age, gender, and the grade of hemorrhoids, there were 100 patients in each group (PPH versus DST). There were no significant differences in the postoperative visual analog scale (VAS) score and analgesic usage. Among complications, the incidence of anorectal stricture was significantly higher in the DST group (p = 0.02). Evaluation of the mucosal specimen showed that the total surface area, the muscle/mucosa ratio and the surface area of the muscle were also significantly higher in the DST group (p = 0.03). Further analysis of the DST group demonstrated that patients with anorectal stricture after surgery are younger than patients without anorectal stricture, and higher muscle/mucosa ratio (p = 0.03) and a higher surface area of the muscle (p = 0.03) also measured in the surgical specimen. The two devices provide similar outcomes of postoperative recovery. Patients who underwent DST stapled hemorrhoidopexy had a higher incidence rate of stricture, larger area of muscle excision, and higher muscle/mucosa ratio in the surgical specimen. Further investigation is warranted for a better understanding of the correlation between muscle excision and anorectal stricture.


Subject(s)
Hemorrhoidectomy/instrumentation , Hemorrhoids/surgery , Surgical Staplers , Acetaminophen/therapeutic use , Anal Canal/pathology , Analgesics/therapeutic use , Anus Diseases/etiology , Constriction, Pathologic/etiology , Equipment Design , Female , Hemorrhage/etiology , Humans , Intestinal Mucosa/pathology , Isoxazoles/therapeutic use , Male , Middle Aged , Organ Size , Pain, Postoperative/drug therapy , Pain, Postoperative/etiology , Pain, Postoperative/prevention & control , Postoperative Complications/etiology , Retrospective Studies , Treatment Outcome , Urinary Retention/etiology
15.
Adv Drug Deliv Rev ; 177: 113928, 2021 10.
Article in English | MEDLINE | ID: covidwho-1355523

ABSTRACT

Infectious diseases continue to inflict a high global disease burden. The consensus is that vaccination is the most effective option against infectious diseases. Oral vaccines have unique advantages in the prevention of global pandemics due to their ease of use, high compliance, low cost, and the ability to induce both systemic and mucosal immune responses. However, challenges of adapting vaccines for oral administration remain significant. Foremost among these are enzymatic and pH-dependent degradation of antigens in the stomach and intestines, the low permeability of mucus barrier, the nonspecific uptake of antigens at the intestinal mucosal site, and the immune suppression result from the elusive immune tolerance mechanisms. Innovative delivery techniques promise great potential for improving the flexibility and efficiency of oral vaccines. A better understanding of the delivery approaches and the immunological mechanisms of oral vaccine delivery systems may provide new scientific insight and tools for developing the next-generation oral vaccine. Here, an overview of the advanced technologies in the field of oral vaccination is proposed, including mucus-penetrating nanoparticle (NP), mucoadhesive delivery vehicles, targeting antigen-presenting cell (APC) nanocarriers and enhanced paracellular delivery strategies and so on. Meanwhile, the mechanisms of delivery vectors interact with mucosal barriers are discussed.


Subject(s)
Drug Delivery Systems , Immunity, Mucosal , Intestinal Mucosa/immunology , Vaccines/administration & dosage , Administration, Oral , Animals , Humans
16.
Front Immunol ; 12: 636966, 2021.
Article in English | MEDLINE | ID: covidwho-1438414

ABSTRACT

Since 2003, the world has been confronted with three new betacoronaviruses that cause human respiratory infections: SARS-CoV, which causes severe acute respiratory syndrome (SARS), MERS-CoV, which causes Middle East respiratory syndrome (MERS), and SARS-CoV-2, which causes Coronavirus Disease 2019 (COVID-19). The mechanisms of coronavirus transmission and dissemination in the human body determine the diagnostic and therapeutic strategies. An important problem is the possibility that viral particles overcome tissue barriers such as the intestine, respiratory tract, blood-brain barrier, and placenta. In this work, we will 1) consider the issue of endocytosis and the possibility of transcytosis and paracellular trafficking of coronaviruses across tissue barriers with an emphasis on the intestinal epithelium; 2) discuss the possibility of antibody-mediated transcytosis of opsonized viruses due to complexes of immunoglobulins with their receptors; 3) assess the possibility of the virus transfer into extracellular vesicles during intracellular transport; and 4) describe the clinical significance of these processes. Models of the intestinal epithelium and other barrier tissues for in vitro transcytosis studies will also be briefly characterized.


Subject(s)
Endocytosis , Intestinal Mucosa/virology , SARS-CoV-2/metabolism , Antibodies, Viral/metabolism , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , COVID-19/drug therapy , COVID-19/transmission , COVID-19/virology , Clinical Trials as Topic , Endocytosis/drug effects , Humans , Intestinal Mucosa/metabolism , Models, Biological , SARS-CoV-2/drug effects , SARS-CoV-2/immunology , Tight Junctions/metabolism , Tight Junctions/virology , Transcytosis/drug effects , Virus Attachment
17.
Clin Dermatol ; 38(6): 750-756, 2020.
Article in English | MEDLINE | ID: covidwho-1385291

ABSTRACT

Pemphigus and its variants, viz., vulgaris, foliaceous, vegetans, Ig A pemphigus, paraneoplastic pemphigus and Senear-Usher syndrome are rare autoimmune blistering diseases of the skin and/or mucous membranes. The autoantibodies involved in the pathogenesis of pemphigus against desmoglein result in the breach of the skin and mucosal barrier, which acts as the first line of defence against pathogens. In this paper we underscore the importance of the integumentary system as a shield against the acquisition as well as transmission of SARS-CoV-2 virion. We have also made an attempt to delineate the various treatment modalities available and the viral-drug dynamics involved in choosing the optimum therapeutic modality.


Subject(s)
Adrenal Cortex Hormones/therapeutic use , COVID-19/transmission , Pemphigus/drug therapy , Virus Shedding , Administration, Oral , Adrenal Cortex Hormones/adverse effects , COVID-19/complications , Feces/virology , Humans , Intestinal Mucosa/drug effects , Intestinal Mucosa/virology , Mouth Mucosa/virology , Pemphigus/complications , Risk Factors , SARS-CoV-2 , Virus Shedding/drug effects
18.
Nat Commun ; 12(1): 134, 2021 01 08.
Article in English | MEDLINE | ID: covidwho-1387323

ABSTRACT

Understanding the factors that contribute to efficient SARS-CoV-2 infection of human cells may provide insights on SARS-CoV-2 transmissibility and pathogenesis, and reveal targets of intervention. Here, we analyze host and viral determinants essential for efficient SARS-CoV-2 infection in both human lung epithelial cells and ex vivo human lung tissues. We identify heparan sulfate as an important attachment factor for SARS-CoV-2 infection. Next, we show that sialic acids present on ACE2 prevent efficient spike/ACE2-interaction. While SARS-CoV infection is substantially limited by the sialic acid-mediated restriction in both human lung epithelial cells and ex vivo human lung tissues, infection by SARS-CoV-2 is limited to a lesser extent. We further demonstrate that the furin-like cleavage site in SARS-CoV-2 spike is required for efficient virus replication in human lung but not intestinal tissues. These findings provide insights on the efficient SARS-CoV-2 infection of human lungs.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , COVID-19/pathology , COVID-19/transmission , Sialic Acids/metabolism , Spike Glycoprotein, Coronavirus/metabolism , Virus Attachment , Animals , Caco-2 Cells , Cell Line, Tumor , Chlorocebus aethiops , Cricetinae , Furin/metabolism , HEK293 Cells , Heparitin Sulfate/metabolism , Humans , Intestinal Mucosa/metabolism , Intestines/virology , Lung/pathology , Lung/virology , SARS-CoV-2/physiology , Severe Acute Respiratory Syndrome/pathology , Vero Cells , Virus Internalization , Virus Replication/physiology
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