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International Journal of Molecular... May 2023Survival in patients with hematological malignancies has improved over the years, both due to major developments in anticancer treatment, as well as in supportive care....
Survival in patients with hematological malignancies has improved over the years, both due to major developments in anticancer treatment, as well as in supportive care. Nevertheless, important and debilitating complications of intensive treatment regimens still frequently occur, including mucositis, fever and bloodstream infections. Exploring potential interacting mechanisms and directed therapies to counteract mucosal barrier injury is of the utmost importance if we are to continue to improve care for this increasingly growing patient population. In this perspective, I highlight recent advances in our understanding of the relation of mucositis and infection.
Topics: Humans; Mucositis; Mucous Membrane; Hematologic Neoplasms; Fever; Hematology
PubMed: 37298545
DOI: 10.3390/ijms24119592 -
Nature Medicine Jul 2020A novel coronavirus-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-emerged in humans in Wuhan, China, in December 2019 and has since disseminated globally....
A novel coronavirus-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-emerged in humans in Wuhan, China, in December 2019 and has since disseminated globally. As of April 16, 2020, the confirmed case count of coronavirus disease 2019 (COVID-19) had surpassed 2 million. Based on full-genome sequence analysis, SARS-CoV-2 shows high homology to SARS-related coronaviruses identified in horseshoe bats. Here we show the establishment and characterization of expandable intestinal organoids derived from horseshoe bats of the Rhinolophus sinicus species that can recapitulate bat intestinal epithelium. These bat enteroids are fully susceptible to SARS-CoV-2 infection and sustain robust viral replication. Development of gastrointestinal symptoms in some patients with COVID-19 and detection of viral RNA in fecal specimens suggest that SARS-CoV-2 might cause enteric, in addition to respiratory, infection. Here we demonstrate active replication of SARS-CoV-2 in human intestinal organoids and isolation of infectious virus from the stool specimen of a patient with diarrheal COVID-19. Collectively, we established the first expandable organoid culture system of bat intestinal epithelium and present evidence that SARS-CoV-2 can infect bat intestinal cells. The robust SARS-CoV-2 replication in human intestinal organoids suggests that the human intestinal tract might be a transmission route of SARS-CoV-2.
Topics: Animals; Betacoronavirus; COVID-19; Cell Differentiation; Cells, Cultured; Child, Preschool; Chiroptera; Chlorocebus aethiops; Coronavirus Infections; Enterocytes; Female; Humans; Infant; Intestinal Mucosa; Intestines; Male; Organoids; Pandemics; Pneumonia, Viral; Reverse Transcriptase Polymerase Chain Reaction; SARS-CoV-2; Vero Cells; Viral Load; Viral Tropism
PubMed: 32405028
DOI: 10.1038/s41591-020-0912-6 -
Frontiers in Immunology 2019Brucellosis is one of the most prevalent bacterial zoonosis of worldwide distribution. The disease is caused by spp., facultative intracellular pathogens. Brucellosis... (Review)
Review
Brucellosis is one of the most prevalent bacterial zoonosis of worldwide distribution. The disease is caused by spp., facultative intracellular pathogens. Brucellosis in animals results in abortion of fetuses, while in humans, it frequently manifests flu-like symptoms and a typical undulant fever, being osteoarthritis a common complication of the chronic infection. The two most common ways to acquire the infection in humans are through the ingestion of contaminated dairy products or by inhalation of contaminated aerosols. spp. enter the body mainly through the gastrointestinal and respiratory mucosa; however, most studies of immune response to spp. are performed analyzing models of systemic immunity. It is necessary to better understand the mucosal immune response induced by infection since this is the main entry site for the bacterium. In this review, some virulence factors and the mechanisms needed for pathogen invasion and persistence are discussed. Furthermore, some aspects of local immune responses induced during infection will be reviewed. With this knowledge, better vaccines can be designed focused on inducing protective mucosal immune response.
Topics: Brucella; Brucellosis; Humans; Immunity, Mucosal; Intestinal Mucosa; Respiratory Mucosa; Virulence
PubMed: 31481953
DOI: 10.3389/fimmu.2019.01759 -
Cellular Immunology Apr 2020The airway mucosa is the primary tissue site exposed to inhaled particulate matter, which includes pathogens and allergens. While most inhaled particles are eliminated... (Review)
Review
The airway mucosa is the primary tissue site exposed to inhaled particulate matter, which includes pathogens and allergens. While most inhaled particles are eliminated from the airways via mucociliary clearance, some pathogens may penetrate the mucosal epithelial barrier and an effective activation of the mucosal immune system is required to prevent further pathogen spread. Similarly, inhaled environmental allergens may induce an aberrant activation of immune cells in the airway mucosa, causing allergic airway disease. During the last years, several investigators employed advanced microscopic imaging on both intravital and tissue explant preparations to observe the dynamic behavior of various immune cells within their complex tissue environment. In the respiratory tract, most imaging studies focused on immune responses of the alveolar compartment in the lung periphery. However, equally important immunological events occur more proximally in the mucosa of the conducting airways, both during infection and allergic responses, calling for a more detailed imaging analysis also at this site. In this review, I will outline the technical challenges of designing microscopic imaging experiments in the conducting airways and summarize our recent efforts in understanding airway mucosal immune cell dynamics in steady-state conditions, during infection and allergy.
Topics: Allergens; Humans; Hypersensitivity; Immune System; Inflammation; Intravital Microscopy; Lung; Microscopy, Fluorescence, Multiphoton; Mucous Membrane; Respiratory Mucosa
PubMed: 30297084
DOI: 10.1016/j.cellimm.2018.10.001 -
Vaccine Jun 2023Coronavirus disease-2019 (COVID-19) is an ongoing pandemic caused by the newly emerged virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Currently,...
Coronavirus disease-2019 (COVID-19) is an ongoing pandemic caused by the newly emerged virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Currently, COVID-19 vaccines are given intramuscularly and they have been shown to evoke systemic immune responses that are highly efficacious towards preventing severe disease and death. However, vaccine-induced immunity wanes within a short time, and booster doses are currently recommended. Furthermore, current vaccine formulations do not adequately restrict virus infection at the mucosal sites, such as in the nasopharyngeal tract and, therefore, have limited capacity to block virus transmission. With these challenges in mind, several mucosal vaccines are currently being developed with the aim of inducing long-lasting protective immune responses at the mucosal sites where SARS-COV-2 infection begins. Past successes in mucosal vaccinations underscore the potential of these developmental stage SARS-CoV-2 vaccines to reduce disease burden, if not eliminate it altogether. Here, we discuss immune responses that are triggered at the mucosal sites and recent advances in our understanding of mucosal responses induced by SARS-CoV-2 infection and current COVID-19 vaccines. We also highlight several mucosal SARS-COV-2 vaccine formulations that are currently being developed or tested for human use and discuss potential challenges to mucosal vaccination.
Topics: Humans; COVID-19 Vaccines; COVID-19; SARS-CoV-2; Cost of Illness; Mucous Membrane; Vaccination
PubMed: 37045682
DOI: 10.1016/j.vaccine.2023.04.013 -
Annual Review of Immunology Apr 2020Mucosal-associated invariant T (MAIT) cells have been attracting increasing attention over the last few years as a potent unconventional T cell subset. Three factors... (Review)
Review
Mucosal-associated invariant T (MAIT) cells have been attracting increasing attention over the last few years as a potent unconventional T cell subset. Three factors largely account for this emerging interest. Firstly, these cells are abundant in humans, both in circulation and especially in some tissues such as the liver. Secondly is the discovery of a ligand that has uncovered their microbial targets, and also allowed for the development of tools to accurately track the cells in both humans and mice. Finally, it appears that the cells not only have a diverse range of functions but also are sensitive to a range of inflammatory triggers that can enhance or even bypass T cell receptor-mediated signals-substantially broadening their likely impact in health and disease. In this review we discuss how MAIT cells display antimicrobial, homeostatic, and amplifier roles in vivo, and how this may lead to protection and potentially pathology.
Topics: Animals; Biomarkers; Disease Susceptibility; Homeostasis; Host-Pathogen Interactions; Humans; Immunity, Mucosal; Mucosal-Associated Invariant T Cells; Mucous Membrane; Signal Transduction; T-Lymphocyte Subsets
PubMed: 31986071
DOI: 10.1146/annurev-immunol-080719-015428 -
BMJ Case Reports Apr 2021A 9-year-old boy presented to the emergency department of a paediatric hospital with non-painful lesions on his lips and inside his mouth, associated with lip swelling....
A 9-year-old boy presented to the emergency department of a paediatric hospital with non-painful lesions on his lips and inside his mouth, associated with lip swelling. On examination, his oral mucosa and lips showed numerous blisters with yellowish serofibrinous content and lip oedema. An eye examination revealed bilateral conjunctival injection. Genitalia was unaffected and no other skin lesions were found. He was on day 4 of clarithromycin prescribed for atypical pneumonia caused by The patient was diagnosed with -associated mucositis and was started on topical treatment with fusidic acid and betamethasone, with gradual improvement of the oral lesions.
Topics: Child; Clarithromycin; Humans; Male; Mouth Mucosa; Mucositis; Mycoplasma pneumoniae; Pneumonia, Mycoplasma
PubMed: 33858884
DOI: 10.1136/bcr-2020-239086 -
International Journal of Molecular... May 2023Oral mucositis (OM) is a common and impactful toxicity of standard cancer therapy, affecting up to 80% of patients. Its aetiology centres on the initial destruction of... (Review)
Review
Oral mucositis (OM) is a common and impactful toxicity of standard cancer therapy, affecting up to 80% of patients. Its aetiology centres on the initial destruction of epithelial cells and the increase in inflammatory signals. These changes in the oral mucosa create a hostile environment for resident microbes, with oral infections co-occurring with OM, especially at sites of ulceration. Increasing evidence suggests that oral microbiome changes occur beyond opportunistic infection, with a growing appreciation for the potential role of the microbiome in OM development and severity. This review collects the latest articles indexed in the PubMed electronic database which analyse the bacterial shift through 16S rRNA gene sequencing methodology in cancer patients under treatment with oral mucositis. The aims are to assess whether changes in the oral and gut microbiome causally contribute to oral mucositis or if they are simply a consequence of the mucosal injury. Further, we explore the emerging role of a patient's microbial fingerprint in OM development and prediction. The maintenance of resident bacteria via microbial target therapy is under constant improvement and should be considered in the OM treatment.
Topics: Humans; RNA, Ribosomal, 16S; Stomatitis; Mouth Mucosa; Neoplasms; Microbiota; Bacteria; Mucositis
PubMed: 37175980
DOI: 10.3390/ijms24098274 -
Frontiers in Immunology 2020Due to direct contact with aquatic environment, mucosal surfaces of teleost fish are continuously exposed to a vast number of pathogens and also inhabited by high... (Review)
Review
Due to direct contact with aquatic environment, mucosal surfaces of teleost fish are continuously exposed to a vast number of pathogens and also inhabited by high densities of commensal microbiota. The B cells and immunoglobulins within the teleost mucosa-associated lymphoid tissues (MALTs) play key roles in local mucosal adaptive immune responses. So far, three Ig isotypes (i.e., IgM, IgD, and IgT/Z) have been identified from the genomic sequences of different teleost fish species. Moreover, teleost Igs have been reported to elicit mammalian-like mucosal immune response in six MALTs: gut-associated lymphoid tissue (GALT), skin-associated lymphoid tissue (SALT), gill-associated lymphoid tissue (GIALT), nasal-associated lymphoid tissue (NALT), and the recently discovered buccal and pharyngeal MALTs. Critically, analogous to mammalian IgA, teleost IgT represents the most ancient Ab class specialized in mucosal immunity and plays indispensable roles in the clearance of mucosal pathogens and the maintenance of microbiota homeostasis. Given these, this review summarizes the current findings on teleost Igs, MALTs, and their immune responses to pathogenic infection, vaccination and commensal microbiota, with the purpose of facilitating future evaluation and rational design of fish vaccines.
Topics: Animals; Fish Diseases; Fish Proteins; Fishes; Gills; Host-Pathogen Interactions; Immunity, Mucosal; Immunization; Immunoglobulin D; Immunoglobulin M; Immunoglobulins; Lymphoid Tissue; Microbiota; Mucous Membrane; Organ Specificity; Peyer's Patches; Vaccination
PubMed: 33123139
DOI: 10.3389/fimmu.2020.567941 -
EBioMedicine Jun 2023Currently approved COVID-19 vaccines administered parenterally induce robust systemic humoral and cellular responses. While highly effective against severe disease,... (Review)
Review
Currently approved COVID-19 vaccines administered parenterally induce robust systemic humoral and cellular responses. While highly effective against severe disease, there is reduced effectiveness of these vaccines in preventing breakthrough infection and/or onward transmission, likely due to poor immunity elicited at the respiratory mucosa. As such, there has been considerable interest in developing novel mucosal vaccines that engenders more localised immune responses to provide better protection and recall responses at the site of virus entry, in contrast to traditional vaccine approaches that focus on systemic immunity. In this review, we explore the adaptive components of mucosal immunity, evaluate epidemiological studies to dissect if mucosal immunity conferred by parenteral vaccination or respiratory infection drives differential efficacy against virus acquisition or transmission, discuss mucosal vaccines undergoing clinical trials and assess key challenges and prospects for mucosal vaccine development.
Topics: Humans; COVID-19 Vaccines; SARS-CoV-2; COVID-19; Vaccines; Mucous Membrane; Vaccination; Immunity, Mucosal; Antibodies, Viral
PubMed: 37146404
DOI: 10.1016/j.ebiom.2023.104585