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Frontiers in Immunology 2019FOXO1 transcription factors affect a number of cell types that are important in the host response. Cell types whose functions are modulated by FOXO1 include... (Review)
Review
FOXO1 transcription factors affect a number of cell types that are important in the host response. Cell types whose functions are modulated by FOXO1 include keratinocytes in the skin and mucosal dermis, neutrophils and macrophages, dendritic cells, Tregs and B-cells. FOXO1 is activated by bacterial or cytokine stimulation. Its translocation to the nucleus and binding to promoter regions of genes that have response elements is stimulated by the MAP kinase pathway and inhibited by the PI3 kinase/AKT pathway. Downstream gene targets of FOXO1 include pro-inflammatory signaling molecules (TLR2, TLR4, IL-1β, and TNF-α), wound healing factors (TGF-β, VEGF, and CTGF) adhesion molecules (integrins-β1, -β3, -β6, αβ, CD11b, CD18, and ICAM-1), chemokine receptors (CCR7 and CXCR2), B cell regulators (APRIL and BLYS), T-regulatory modulators (Foxp3 and CTLA-4), antioxidants (GPX-2 and cytoglobin), and DNA repair enzymes (GADD45α). Each of the above cell types are found in oral mucosa and modulated by bacteria or an inflammatory microenvironment. FOXO1 contributes to the regulation of these cells, which collectively maintain and repair the epithelial barrier, formation and activation of Tregs that are needed to resolve inflammation, mobilization, infiltration, and activation of anti-bacterial defenses in neutrophils, and the homing of dendritic cells to lymph nodes to induce T-cell and B-cell responses. The goal of the manuscript is to review how the transcription factor, FOXO1, contributes to the activation and regulation of key leukocytes needed to maintain homeostasis and respond to bacterial challenge in oral mucosal tissues. Examples are given with an emphasis on lineage specific deletion of to explore the impact of FOXO1 on cell behavior, inflammation and susceptibility to infection.
Topics: Animals; Dendritic Cells; Disease Susceptibility; Forkhead Box Protein O1; Gene Expression Regulation; Humans; Immunity, Mucosal; Lymphocytes; Macrophages; Monocytes; Mucous Membrane; Periodontal Diseases; Signal Transduction
PubMed: 31849924
DOI: 10.3389/fimmu.2019.02530 -
Otolaryngology--head and Neck Surgery :... Mar 2023To assess for differences in surgical site infection (SSI) rates and bacterial load after major mucosal head and neck surgery between patients who received topical... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To assess for differences in surgical site infection (SSI) rates and bacterial load after major mucosal head and neck surgery between patients who received topical antimicrobial prophylaxis and those who did not.
DATA SOURCES
Ovid Medline, Embase, SCOPUS, Cochrane Library, and ClinicalTrials.gov from inception to May 20, 2021, with cross-referencing of retrieved studies per PRISMA guidelines.
REVIEW METHODS
Inclusion criteria captured clinical trials, cohort studies, and case-control studies with infectious outcomes of adults who underwent major mucosal head and neck surgery and received perioperative topical antimicrobial therapy to the oral cavity and/or pharynx. Studies of dental procedures were excluded. The primary outcome was SSI rate, and the secondary outcome was bacterial load. Two blinded investigators screened each text.
RESULTS
Of 265 unique citations, 9 studies of 470 total patients were included. Topical treatments included numerous antibiotics and antiseptics directly applied over mucosa. Pooled SSI rates of 252 patients in the intervention cohort and 218 in the control cohort were 8% (95% CI, 3%-14%; I = 61.2%) and 29% (95% CI, 16%-43%; I = 79.5%), respectively. A meta-analysis of 7 comparative studies totaling 192 patients receiving topical therapy and 218 control patients revealed a pooled relative risk of 0.44 (95% CI, 0.28-0.68; I = 0.0%) in favor of the treatment group. The studies demonstrated a short-term decrease in bacterial counts after topical antimicrobial prophylaxis.
CONCLUSION
Patients who underwent prophylactic topical antimicrobial therapy had less than half the risk of developing SSI after mucosal head and neck surgery when compared with those who received no topical prophylaxis.
Topics: Adult; Humans; Anti-Infective Agents; Anti-Bacterial Agents; Surgical Wound Infection; Antibiotic Prophylaxis; Infection Control; Mucous Membrane
PubMed: 35608917
DOI: 10.1177/01945998221100801 -
Viruses May 2023The main objectives were to describe the prevalence of HPV, its genotypes and HPV-associated dysplastic lesions in the oropharyngeal mucosa of PLHIV and related factors.
BACKGROUND
The main objectives were to describe the prevalence of HPV, its genotypes and HPV-associated dysplastic lesions in the oropharyngeal mucosa of PLHIV and related factors.
MATERIAL AND METHODS
This cross-sectional prospective study consecutively enrolled PLHIV attending our specialist outpatient units. At visit, HIV-related clinical and analytical variables were gathered, and oropharyngeal mucosa exudates were taken to detect HPV and other STIs by polymerase chain reaction. Samples were also taken from the anal canal of all participants and from the genital mucosa of the women for HPV detection/genotyping and cytological study.
RESULTS
The 300 participants had a mean age of 45.1 years; 78.7% were MSM and 21.3% women; 25.3% had a history of AIDS; 99.7% were taking ART; and 27.3% had received an HPV vaccine. HPV infection prevalence in the oropharynx was 13%, with genotype 16 being the most frequent (2.3%), and none had dysplasia. Simultaneous infection with (HR: 4.02 (95% CI: 1.06-15.24)) and a history of anal HSIL or SCCA (HR: 21.52 (95% CI: 1.59-291.6)) were risk factors for oropharyngeal HPV infection, whereas ART duration (8.8 vs. 7.4 years) was a protective factor (HR: 0.989 (95% CI: 0.98-0.99)).
CONCLUSIONS
The prevalence of HPV infection and dysplasia was low in the oropharyngeal mucosae. A higher exposure to ART was protective against oral HPV infection.
Topics: Male; Humans; Female; Middle Aged; Anal Canal; Papillomavirus Infections; HIV Infections; Homosexuality, Male; Cross-Sectional Studies; Prospective Studies; Papillomaviridae; Risk Factors; Mucous Membrane; Genotype; Hyperplasia; Oropharynx; Genitalia; Prevalence
PubMed: 37243256
DOI: 10.3390/v15051170 -
Mucosal Immunology Jul 2021The urinary tract consists of the bladder, ureters, and kidneys, and is an essential organ system for filtration and excretion of waste products and maintaining systemic... (Review)
Review
The urinary tract consists of the bladder, ureters, and kidneys, and is an essential organ system for filtration and excretion of waste products and maintaining systemic homeostasis. In this capacity, the urinary tract is impacted by its interactions with other mucosal sites, including the genitourinary and gastrointestinal systems. Each of these sites harbors diverse ecosystems of microbes termed the microbiota, that regulates complex interactions with the local and systemic immune system. It remains unclear whether changes in the microbiota and associated metabolites may be a consequence or a driver of urinary tract diseases. Here, we review the current literature, investigating the impact of the microbiota on the urinary tract in homeostasis and disease including urinary stones, acute kidney injury, chronic kidney disease, and urinary tract infection. We propose new avenues for exploration of the urinary microbiome using emerging technology and discuss the potential of microbiome-based medicine for urinary tract conditions.
Topics: Animals; Disease Management; Disease Susceptibility; Feedback, Physiological; Gastrointestinal Microbiome; Homeostasis; Host Microbial Interactions; Host-Pathogen Interactions; Humans; Metagenome; Metagenomics; Microbiota; Mucous Membrane; Organ Specificity; Urinary Tract Infections
PubMed: 33542492
DOI: 10.1038/s41385-020-00372-5 -
Proceedings of the National Academy of... Feb 2023Rotaviruses (RVs) preferentially replicate in the small intestine and frequently cause severe diarrheal disease, and the following enteric infection generally induces...
Rotaviruses (RVs) preferentially replicate in the small intestine and frequently cause severe diarrheal disease, and the following enteric infection generally induces variable levels of protective systemic and mucosal immune responses in humans and other animals. Rhesus rotavirus (RRV) is a simian RV that was previously used as a human RV vaccine and has been extensively studied in mice. Although RRV replicates poorly in the suckling mouse intestine, infection induces a robust and protective antibody response. The recent availability of plasmid only-based RV reverse genetics systems has enabled the generation of recombinant RVs expressing foreign proteins. However, recombinant RVs have not yet been experimentally tested as potential vaccine vectors to immunize against other gastrointestinal pathogens in vivo This is a newly available opportunity because several live-attenuated RV vaccines are already widely administered to infants and young children worldwide. To explore the feasibility of using RV as a dual vaccine vector, we rescued replication-competent recombinant RRVs harboring bicistronic gene segment 7 that encodes the native RV nonstructural protein 3 (NSP3) protein and a human norovirus (HuNoV) VP1 protein or P domain from the predominant genotype GII.4. The rescued viruses expressed HuNoV VP1 or P protein in infected cells in vitro and elicited systemic and local antibody responses to HuNoV and RRV following oral infection of suckling mice. Serum IgG and fecal IgA from infected suckling mice bound to and neutralized both RRV and HuNoV. These findings have encouraging practical implications for the design of RV-based next-generation multivalent enteric vaccines to target HuNoV and other human enteric pathogens.
Topics: Child; Infant; Humans; Animals; Mice; Child, Preschool; Rotavirus; Antibodies, Neutralizing; Rotavirus Infections; Norovirus; Mucous Membrane; Antibodies, Viral
PubMed: 36821582
DOI: 10.1073/pnas.2214421120 -
Bulletin Du Cancer 2021Mucositis is defined as inflammatory and/or ulcerative lesions of the oral and/or gastrointestinal tract. It occurs in approximately 40% to 50% of adults patients... (Review)
Review
Mucositis is defined as inflammatory and/or ulcerative lesions of the oral and/or gastrointestinal tract. It occurs in approximately 40% to 50% of adults patients receiving conventional chemotherapy and up to 75% of patients receiving high dose chemotherapy as conditioning for hematopoietic stem cell transplantation. It is a toxic side effect, which strongly impairs quality of life and leads to refractory pain, increasing risk of infection and even therapeutic modifications. Despite improvements made, the management of mucositis remains a challenge and is still not consensual. A multicentric survey of practices concerning the preventive and curative management of chemo-induced mucositis in pediatric oncology department in France was carried out using a standardized questionnaire. Results confirm heterogeneous practices and the small progress made during the last decade. This national survey and an analysis of the recent literature leads to propose guidelines for the prevention and treatment of oral mucositis in children receiving treatment for cancer.
Topics: Antineoplastic Agents; Cancer Care Facilities; Child; France; Health Care Surveys; Hematopoietic Stem Cell Transplantation; Humans; Laser Therapy; Mucositis; Oral Hygiene; Pain Management; Practice Patterns, Physicians'; Quality of Life; Transplantation Conditioning
PubMed: 33933290
DOI: 10.1016/j.bulcan.2021.01.018 -
The New England Journal of Medicine Oct 2023
Topics: Humans; Antibodies, Neutralizing; Antibodies, Viral; Mucous Membrane; SARS-CoV-2; COVID-19
PubMed: 37888924
DOI: 10.1056/NEJMc2310347 -
International Journal of Molecular... Feb 2022Bacteria and viruses are both important pathogens causing intestinal infections, and studies on their pathogenic mechanisms tend to focus on one pathogen alone. However,... (Review)
Review
Bacteria and viruses are both important pathogens causing intestinal infections, and studies on their pathogenic mechanisms tend to focus on one pathogen alone. However, bacterial and viral co-infections occur frequently in clinical settings, and infection by one pathogen can affect the severity of infection by another pathogen, either directly or indirectly. The presence of synergistic or antagonistic effects of two pathogens in co-infection can affect disease progression to varying degrees. The triad of bacterial-viral-gut interactions involves multiple aspects of inflammatory and immune signaling, neuroimmunity, nutritional immunity, and the gut microbiome. In this review, we discussed the different scenarios triggered by different orders of bacterial and viral infections in the gut and summarized the possible mechanisms of synergy or antagonism involved in their co-infection. We also explored the regulatory mechanisms of bacterial-viral co-infection at the host intestinal immune interface from multiple perspectives.
Topics: Animals; Bacterial Infections; Coinfection; Humans; Immunity, Mucosal; Intestinal Mucosa; Virus Diseases
PubMed: 35216425
DOI: 10.3390/ijms23042311 -
Cytokine Oct 2021Interleukin-17C (IL-17C) is an understudied member of the IL-17 family of cytokines. Its synthesis is induced by both cytokines and pathogenic stimuli in a variety of... (Review)
Review
Interleukin-17C (IL-17C) is an understudied member of the IL-17 family of cytokines. Its synthesis is induced by both cytokines and pathogenic stimuli in a variety of cell types, most often expressed at mucosal and barrier surfaces. IL-17C expression is dysregulated in a variety of autoinflammatory and autoimmune diseases including inflammatory bowel disease, psoriasis, and atopic dermatitis, yet it is protective against bacterial infections of the gut, skin, and lungs. In this review we highlight studies on IL-17C regulation and its function at human mucosal surfaces. Understanding the relationship between IL-17C and autoinflammatory and autoimmune diseases of the mucosa and defining the beneficial and pathogenic functions of the cytokine in inflammatory responses are the first steps in determining the potential for IL-17C as a therapeutic target.
Topics: Animals; Humans; Immunity, Mucosal; Interleukin-17; Models, Biological; Mucous Membrane; Signal Transduction
PubMed: 34293699
DOI: 10.1016/j.cyto.2021.155641 -
JCI Insight Sep 2023Understanding mucosal antibody responses from SARS-CoV-2 infection and/or vaccination is crucial to develop strategies for longer term immunity, especially against...
Understanding mucosal antibody responses from SARS-CoV-2 infection and/or vaccination is crucial to develop strategies for longer term immunity, especially against emerging viral variants. We profiled serial paired mucosal and plasma antibodies from COVID-19 vaccinated only vaccinees (vaccinated, uninfected), COVID-19-recovered vaccinees (recovered, vaccinated), and individuals with breakthrough Delta or Omicron BA.2 infections (vaccinated, infected). Saliva from COVID-19-recovered vaccinees displayed improved antibody-neutralizing activity, Fcγ receptor (FcγR) engagement, and IgA levels compared with COVID-19-uninfected vaccinees. Furthermore, repeated mRNA vaccination boosted SARS-CoV-2-specific IgG2 and IgG4 responses in both mucosa biofluids (saliva and tears) and plasma; however, these rises only negatively correlated with FcγR engagement in plasma. IgG and FcγR engagement, but not IgA, responses to breakthrough COVID-19 variants were dampened and narrowed by increased preexisting vaccine-induced immunity against the ancestral strain. Salivary antibodies delayed initiation following breakthrough COVID-19 infection, especially Omicron BA.2, but rose rapidly thereafter. Importantly, salivary antibody FcγR engagements were enhanced following breakthrough infections. Our data highlight how preexisting immunity shapes mucosal SARS-CoV-2-specific antibody responses and has implications for long-term protection from COVID-19.
Topics: Humans; COVID-19; Breakthrough Infections; SARS-CoV-2; Receptors, IgG; Immunoglobulin G; Antibodies, Viral; Mucous Membrane
PubMed: 37737263
DOI: 10.1172/jci.insight.172470