Melissa Linehan
A5053660262- Immunotherapy and Immune Responses
- interferon and immune responses
- Immune Response and Inflammation
- T-cell and B-cell Immunology
- Herpesvirus Infections and Treatments
- COVID-19 Clinical Research Studies
- Immune Cell Function and Interaction
- COVID-19 diagnosis using AI
- SARS-CoV-2 and COVID-19 Research
- Long-Term Effects of COVID-19
- SARS-CoV-2 detection and testing
- Cytokine Signaling Pathways and Interactions
- Viral Infections and Immunology Research
- Viral gastroenteritis research and epidemiology
- Influenza Virus Research Studies
- Parvovirus B19 Infection Studies
- Immune cells in cancer
- Dental Research and COVID-19
- Glycosylation and Glycoproteins Research
- Machine Learning in Healthcare
- Vector-Borne Animal Diseases
- Clostridium difficile and Clostridium perfringens research
- Metabolomics and Mass Spectrometry Studies
- Inflammasome and immune disorders
- COVID-19 Impact on Reproduction
Duke University
2023
Yale University
2009-2022
General Department of Preventive Medicine
2009
RIKEN Center for Integrative Medical Sciences
2006
There is increasing evidence that coronavirus disease 2019 (COVID-19) produces more severe symptoms and higher mortality among men than women1–5. However, whether immune responses against acute respiratory syndrome (SARS-CoV-2) differ between sexes, such differences correlate with the sex difference in course of COVID-19, currently unknown. Here we examined viral loads, SARS-CoV-2-specific antibody titres, plasma cytokines blood-cell phenotyping patients moderate COVID-19 who had not...
Herpes simplex virus (HSV) type 2 infection occurs primarily at the genital mucosal surfaces and is a leading cause of ulcerative lesions. Despite availability animal models for HSV-2 infection, little known regarding mechanism immune induction within vaginal mucosa. Here, we examined cell types responsible initiation protective Th1 immunity to HSV-2. Intravaginal inoculation led rapid recruitment submucosal dendritic cells (DCs) infected epithelium. Subsequently, CD11c+ DCs harboring viral...
Location Matters Plasmacytoid dendritic cells (pDCs), an immune cell specialized to respond viral infections, use Toll-like receptors (TLRs) 7 and 9 expressed in endosomes sense nucleic acids. Triggering of TLR7 or results the induction two distinct signaling pathways, one that leads production proinflammatory cytokines another induces expression antiviral type I interferons. How receptor can trigger however, is not clear. Sasai et al. (p. 1530 ) now show subcellular localization key. Cells...
Abstract Rapid and accurate SARS-CoV-2 diagnostic testing is essential for controlling the ongoing COVID-19 pandemic. The current gold standard diagnosis real-time RT-PCR detection of from nasopharyngeal swabs. Low sensitivity, exposure risks to healthcare workers, global shortages swabs personal protective equipment, however, necessitate validation new approaches. Saliva a promising candidate diagnostics because (1) collection minimally invasive can reliably be self-administered (2) saliva...
Abstract Although microbial populations in the gut microbiome are associated with COVID-19 severity, a causal impact on patient health has not been established. Here we provide evidence that dysbiosis is translocation of bacteria into blood during COVID-19, causing life-threatening secondary infections. We first demonstrate SARS-CoV-2 infection induces mice, which correlated alterations to Paneth cells and goblet cells, markers barrier permeability. Samples collected from 96 patients at two...
Dendritic cells (DCs) express multiple Toll-like receptors (TLR) in distinct cellular locations. Herpes simplex viruses (HSV) have been reported to engage both the surface TLR2 and intracellular TLR9 conventional DCs. However, contributions of these TLRs recognition HSV induction proinflammatory cytokines DCs remain unclear. Here, we demonstrate that a rare population HSV, laboratory strains primary clinical isolates from humans, has capacity activate TLR2. This virus is recognized through...
Abstract Dendritic cells (DCs) are powerful APCs capable of activating naive lymphocytes. Of the DC subfamilies, plasmacytoid DCs (pDCs) unique in that they secrete high levels type I IFNs response to viruses but their role inducing adaptive immunity remains divisive. In this study, we examined importance pDCs and ability recognize a virus through TLR9 against genital HSV-2 infection. We show low number survey vaginal mucosa at steady state. Upon infection, recruited vagina produce large...
Although the importance of cytotoxic T lymphocytes and neutralizing antibodies for antiviral defense is well known, mechanism Th1 remains unclear. We show that cells mediate noncytolytic protection independent direct lysis through local secretion IFN-γ after herpes simplex virus (HSV) 2 infection. acted on stromal cells, but not hematopoietic to prevent further viral replication spread throughout vaginal mucosa. Importantly, unlike other known mechanisms, this effector function did require...
Although mucosal surfaces represent the main portal of entry for pathogens, mechanism antigen presentation by dendritic cells (DCs) that patrol various tissues remains unclear. Instead, much effort has focused on understanding initiation immune responses generated against antigens delivered injection. We examined contributions migratory versus lymph node–resident DC populations in to CD4 and CD8 T after needle injection, epicutaneous infection, or vaginal herpes simplex virus (HSV) 1...
Short stem-loop RNAs activate RIG-I in mice, activating the innate immune system via specific patterns of gene expression.
As SARS-CoV-2 continues to cause morbidity and mortality around the world, there is an urgent need for development of effective medical countermeasures. Here, we assessed antiviral capacity a minimal RIG-I agonist, stem-loop RNA 14 (SLR14), in viral control, disease prevention, post-infection therapy, cross-variant protection mouse models infection. A single dose SLR14 prevented infection lower respiratory tract severe type I interferon (IFN-I)–dependent manner. demonstrated remarkable...
Abstract The follicle-associated epithelium (FAE) secretes chemokines important in the recruitment of various cell types including CCL20 (MIP-3α). is chemotactic to CD11b+ dendritic cells (DCs) distributed subepithelial dome regions Peyer’s patches, and mice deficient receptor for CCL20, CCR6, have been reported be devoid DCs regions. Here, we describe another chemokine specifically secreted from FAE mouse CCL9 (MIP-1γ, CCF18, MRP-2). By situ hybridization, demonstrated that mRNA was...
Highlights•5′-p RNAs, which are common host actively antagonize signaling by RIG-I•RIG-I discriminates between RNA ligands that differ only a single phosphate•RIG-I forms distinct interaction networks with RNAs bearing different 5′ termini•The RIG-I Hel2 loop acts as gate to prevent 5′-p (host RNAs) from signalingSummaryThe innate immune sensor must sensitively detect and respond viral enter the cytoplasm, while remaining unresponsive abundance of structurally similar products metabolism. In...
Oral transmission of poliovirus is restricted to humans and certain primate species. The expression the human receptor (CD155) within gastrointestinal-associated lymphoid tissues from species that are susceptible (human) or resistant (rhesus macaque CD155 transgenic [Tg] mice) oral infection was examined. Sensitivity correlated with not only in intestinal epithelium, including follicle-associated epithelium (FAE) microfold (M) cells Peyer's patches, but also germinal centers patches. rhesus...
Dendritic cells (DCs) represent key professional antigen-presenting capable of initiating primary immune responses. A specialized subset DCs, the Langerhans (LCs), are located in stratified squamous epithelial layer skin and within mucosal lining vaginal oral cavities. The mucosa undergoes cyclic changes under control sex hormones, renewal characteristics DCs (VEDCs) remain unknown. Here, we examined origin VEDCs. In contrast to epidermal LCs, epithelium vagina were found be repopulated...
Significance Chilblain diagnoses have increased during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic and been attributed to viral infection a subsequent robust antiviral immune response. As result, providers managed these cases differently than idiopathic chilblains, which are associated with cold exposure. The relationship between chilblains SARS-CoV-2 infection, however, remains unclear as most patients do not test positive for SARS-CoV-2–specific PCR or...
ABSTRACT Herpes simplex virus type 2 (HSV-2) is transmitted through the genital mucosa during sexual encounters. In recent years, HSV-1 has also become commonly associated with primary herpes. The mechanism of viral entry and HSV-2 in female tract unknown. order to understand molecular interactions required for HSV into vaginal epithelium, we examined expression herpesvirus mediator nectin-1 vagina human mouse at different stages their hormonal cycle. Nectin-1 was highly expressed epithelium...
Within the complex environment of human cell, RIG-I innate immune receptor must detect presence double-stranded viral RNA molecules and differentiate them from a diversity host molecules. In an ongoing effort to understand molecular basis for target specificity, here, we evaluate ability this sensor respond triphosphorylated, that contain all possible terminal base pairs common mismatches. addition, test response duplexes with various types 5' 3' overhangs. We conducted quantitative...