A5041065076- Immune Response and Inflammation
- Immunotherapy and Immune Responses
- SARS-CoV-2 and COVID-19 Research
- Escherichia coli research studies
- Influenza Virus Research Studies
- Viral gastroenteritis research and epidemiology
- Respiratory viral infections research
- Immune Cell Function and Interaction
- Pneumonia and Respiratory Infections
- Neonatal Respiratory Health Research
- RNA Interference and Gene Delivery
- vaccines and immunoinformatics approaches
- Bacillus and Francisella bacterial research
- T-cell and B-cell Immunology
- Vector-borne infectious diseases
- Viral Infections and Vectors
- Cancer-related molecular mechanisms research
- interferon and immune responses
- Toxin Mechanisms and Immunotoxins
- Immune cells in cancer
- Streptococcal Infections and Treatments
- Alcoholism and Thiamine Deficiency
- Organophosphorus compounds synthesis
- Metabolomics and Mass Spectrometry Studies
- Inflammasome and immune disorders
Massachusetts General Hospital
2019-2025
Broad Institute
2021-2025
Harvard University
2019-2022
Seoul National University
2007-2021
Massachusetts Institute of Technology
2021
International Vaccine Institute
2005-2018
Abstract Multiple studies have established associations between human gut bacteria and host physiology, but determining the molecular mechanisms underlying these has been challenging 1–3 . Akkermansia muciniphila robustly associated with positive systemic effects on metabolism, favourable outcomes to checkpoint blockade in cancer immunotherapy homeostatic immunity 4–7 Here we report identification of a lipid from A. ’s cell membrane that recapitulates immunomodulatory activity cell-based...
It has been difficult to evaluate the protective efficacy of vaccine candidates against shigellosis, a major form bacillary dysentery caused by Shigella spp. infection, because lack suitable animal models. To develop proper model representing human dysentery, guinea pigs were challenged with virulent flexneri serotype 2a (strains 2457T or YSH6000) S. 5a (strain M90T) intrarectal (i.r.) route. Interestingly, all administered these strains developed severe and acute rectocolitis. They lost...
Background The ectodomain of matrix protein 2 (M2e) influenza A virus is a rationale target antigen candidate for the development universal vaccine against as M2e undergoes little sequence variation amongst human strains. Vaccine-induced M2e-specific antibodies (Abs) have been shown to display significant cross-protective activity in animal models. M2e-based constructs be more protective when administered by intranasal (i.n.) route than after parenteral injection. However, i.n....
Highlights•Microtubule destabilization in dendritic cells drives DC maturation and T cell activation•GEF-H1 is released from microtubules, leading to its release triggers the RhoA-JNK-c-Jun signaling axis AP-1 transcriptional response•GEF-H1 critical for maturation, antigen cross-presentation, anti-tumor immunitySummaryDendritic (DC) activation a step responses. Certain chemotherapeutics can influence function. Here we demonstrate that chemotherapy capable of microtubule has direct effects...
An systematic phenotypic screen of the mouse gut microbiome for metabolites with an immunomodulatory effect identified Muribaculum intestinale as one only two members oversized on T-cell populations. Here we report identification and characterization a lipid, MiCL-1, responsible metabolite. MiCL-1 is 18:1-16:0 cardiolipin, whose close relatives are found concave lipid surfaces both mammals bacteria. was synthesized to confirm structural analysis functionally characterized in cell-based...
Abstract Background Immunization with the spike protein (S) of severe acute respiratory syndrome (SARS)-coronavirus (CoV) in mice is known to produce neutralizing antibodies and prevent infection caused by SARS-CoV. Polyethylenimine 25K (PEI) a cationic polymer which effectively delivers plasmid DNA. Results In present study, immune responses BALB/c immunized via intranasal (i.n.) route SARS DNA vaccine (pci-S) PEI/pci-S complex form have been examined. The size nanoparticles appeared be...
Since being domesticated about 10,000–12,000 years ago, domestic pigs (Sus scrofa domesticus) have been selected for traits of economic importance, in particular large body size. However, Yucatan miniature small size to withstand high temperature environment and laboratory use. This renders the pig a valuable model understanding evolution We investigate genetic signature selection pig. Phylogenetic distance was compared other swine breeds (Yorkshire, Landrace, Duroc wild boar). By estimating...
Coley's toxins, an early and enigmatic form of cancer (immuno)therapy, were based on preparations Streptococcus pyogenes. As part a program to explore bacterial metabolites with immunomodulatory potential, S. pyogenes assayed in cell-based immune assay, single membrane lipid, 18:1/18:0/18:1/18:0 cardiolipin, was identified. Its activity profiled additional cellular assays, which showed it be agonist TLR2–TLR1 signaling pathway 6 μM EC50 robust TNF-α induction. A synthetic analog switched...
Abstract Low-pathogenicity avian influenza H9N2 remains an endemic disease worldwide despite continuous vaccination, indicating the need for improved vaccine strategy. Bacillus subtilis ( B. ), a gram-positive and endospore-forming bacterium, is non-pathogenic species that has been used in probiotic formulations both animals humans. The objective of present study was to elucidate effect spores as adjuvants chickens administered inactivated virus H9N2. Herein, adjuvanticity demonstrated by...
A multifactorial association study detected a probable causal connection between the prevalence of Morganella morganii in gut microbiome and incidence major depressive disorder (MDD) human host. bioassay-guided fractionation approach identified bacterially produced metabolites that induced pro-inflammatory immune responses. The are unusual phospholipids resemble conventional cardiolipins, which diethanolamine (DEA) replaces central glycerol. These molecular chimeras endogenous from...
Salmonella organisms are Gram negative and facultative anaerobic bacteria that cause typhoid fever in humans. In this study, we evaluated LPS-specific adaptive immunity innate immune-deficient mice after oral administration of attenuated enterica serovar Typhimurium (S. Typhimurium) strains. Of interest, identical levels IgG IgA Abs were elicited the systemic (i.e., serum spleen) mucosal fecal extract small intestine) compartments wild-type, TLR4(-/-), MyD88(-/-) following vaccination with...
Abstract The most common enteric colibacillosis in neonatal and newborns is caused by enterotoxigenic Escherichia coli (ETEC). Colonization of ETEC the small intestine associated with adhesions using fimbriae, which known as a specific adhesion factor provides highly means for anchoring prerequisite an infectious agent. In present study we have engineered Lactobacillus acidophilus to produce recombinant K99 used colonization pigs. expression fimbrial protein was confirmed SDS‐PAGE,...
Abstract TLRs directly induce innate host defense responses, but the mechanisms of TLR-mediated adaptive immunity remain subject to debate. In this study, we clarified a role for induction by oral vaccination with live recombinant attenuated Salmonella enteric serovar Typhimurium vaccine (RASV) strain expressing Streptococcus pneumoniae surface protein A (PspA) Ag. Of note, or intranasal RASV PspA resulted in identical even significantly higher levels PspA-specific IgG and IgA responses...
Organic acids have long been known for their beneficial effects on growth performance in domestic animals. However, impact immune responses against viral antigens chickens is unclear. The present study aimed to investigate immunological parameters broilers immunized with a H9N2 vaccine and/or fed diet containing organic (citric, formic, and lactic acids). We allotted 1-day-old into 4 groups: control (C), supplemented (O), administered (V), (OV). Blood spleen samples were taken at 2, 7 14 d...
The human immune system detects potentially pathogenic microbes with receptors that respond to microbial metabolites. While the overall signaling pathway is known in considerable detail, initial molecular signals, microbially produced immunogens, for important diseases like Lyme disease (LD) are often not well-defined. immunogens LD by spirochete Borrelia burgdorferi, and a galactoglycerolipid (1) has been identified as key trigger inflammatory response characterizes LD. This report corrects...
Respiratory syncytial virus (RSV) is a major pathogen that infects lower respiratory tract and causes common disease. Despite serious pathological consequences with this virus, effective treatments for controlling RSV infection remain unsolved, along poor innate immune responses induced at the initial stage of infection. Such defense mechanism against leads us to study role alveolar macrophage (AM) one primary cell types in may contribute protective As an strategy enhancing anti-viral...
Abstract The innate immune response following infection with entero-invasive bacterial species is triggered upon release of cyclic di-guanylate monophosphate (c-di-GMP) into the host cell cytosol. Bacterial c-di-GMP activates intracellular Sensor Stimulator Interferon Genes (STING), encoded by Tmem173 in mice. Here we identify Regulatory Factor (IRF) 1 as a critical effector STING-mediated microbial DNA sensing that responsible for T H 17 generation mucosal system. We find STING activation...
Probiotics can be an effective treatment for atopic dermatitis (AD), while their mechanism of action is still unclear. Here, we induced AD in mice with 2,4-dinitrochlorobenzene and administrated YK4, a probiotic mixture consisting Lactobacillus acidophilus CBT LA1, L. plantarum LP3, Bifidobacterium breve BR3, B. lactis BL3. Then, have validated the underlying alleviation by YK4 from intestinal systematic immunological perspectives. Administration alleviated symptoms suppressing expression...