A5028441273- Immune Response and Inflammation
- Leprosy Research and Treatment
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Sepsis Diagnosis and Treatment
- Inflammation biomarkers and pathways
- Immune cells in cancer
- Mycobacterium research and diagnosis
- Systemic Lupus Erythematosus Research
- Neonatal and Maternal Infections
- Immunotherapy and Immune Responses
- Cytokine Signaling Pathways and Interactions
- Monoclonal and Polyclonal Antibodies Research
- Tuberculosis Research and Epidemiology
- Neuroinflammation and Neurodegeneration Mechanisms
- Soft tissue tumor case studies
- Connective tissue disorders research
- Dupuytren's Contracture and Treatments
- Pharmacological Effects of Natural Compounds
- Erythrocyte Function and Pathophysiology
- Sphingolipid Metabolism and Signaling
- Psoriasis: Treatment and Pathogenesis
- Neonatal Respiratory Health Research
- interferon and immune responses
- Dermatological and COVID-19 studies
University of California, Los Angeles
2013-2024
Broad Center
2024
California NanoSystems Institute
2024
APLA Health
2015
University of Florida
2007-2014
Florida College
2010-2014
UF Health Shands Hospital
2010
Center for Rheumatology
2008
Autoimmune Technologies (United States)
2008
Polymicrobial sepsis alters the adaptive immune response and induces T cell suppression Th2 polarization. We identify a GR-1+CD11b+ population whose numbers dramatically increase remain elevated in spleen, lymph nodes, bone marrow during polymicrobial sepsis. Phenotypically, these cells are heterogeneous, immature, predominantly myeloid progenitors that express interleukin 10 several other cytokines chemokines. Splenic GR-1+ effectively suppress antigen-specific CD8+ interferon (IFN) γ...
Interfering with Interferons Infections Mycobacteria, including Mycobacterium leprae or M. tuberculosis , vary substantially in their clinical presentation. For instance, some cases of the infection is self-healing very few lesions. In contrast, people experience disseminated form, where skin lesions abound and bacteria are abundant. patients infected Teles et al. (p. 1448 published online 28 February) found that disease associates a type I interferon gene signature, whereas form II...
Increased type I interferon (IFN-I) production and IFN-stimulated gene (ISG) expression are linked to the pathogenesis of systemic lupus erythematosus (SLE). Although mechanisms responsible for dysregulated IFN-I in SLE remain unclear, autoantibody-mediated uptake endogenous nucleic acids is thought play a role. 2,6,10,14-tetramethylpentadecane (TMPD; also known as pristane) induces lupus-like disease mice characterized by immune complex nephritis with autoantibodies DNA ribonucleoproteins....
Abstract Objective Systemic lupus erythematosus (SLE) is diagnosed according to a spectrum of clinical manifestations and autoantibodies associated with abnormal expression type I interferon (IFN‐I)–stimulated genes (ISGs). The role IFN‐I in the pathogenesis SLE remains uncertain, partly due lack suitable animal models. objective this study was examine signaling murine induced by 2,6,10,14‐tetramethylpentadecane (TMPD). Methods receptor–deficient (IFNAR −/− ) 129Sv mice wild‐type (WT)...
Sepsis, the systemic inflammatory response to microbial infection, induces changes in both innate and adaptive immunity that presumably lead increased susceptibility secondary infections, multiorgan failure, death. Using a model of murine polymicrobial sepsis whose severity approximates human sepsis, we examined outcomes defined requirements for survival after Pseudomonas aeruginosa pneumonia or disseminated Listeria monocytogenes infection. We demonstrate early neutrophil numbers function...
Microbes activate pattern recognition receptors to initiate adaptive immunity. T cells affect early innate inflammatory responses viral infection, but both activation and suppression have been demonstrated. We identify a novel role for B in the immune response during bacterial sepsis. demonstrate that Rag1−/− mice display deficient reduced survival Interestingly, cell–deficient or anti-CD20 cell–depleted mice, not α/β decreased cytokine chemokine production after Both treatment of with serum...
Neutrophils are essential for successful host eradication of bacterial pathogens and survival to polymicrobial sepsis. During inflammation, the bone marrow provides a large reserve neutrophils that released into peripheral circulation where they traverse sites infection. Although survival, few studies have investigated mechanisms responsible neutrophil mobilization from during Using cecal ligation puncture model sepsis, we demonstrated is not dependent on TLR4, MyD88, TRIF, IFNARα/β, or...
Mycobacterium leprae causes leprosy and is unique among mycobacterial diseases in producing peripheral neuropathy. This debilitating morbidity attributed to axon demyelination resulting from direct interaction of the M. leprae-specific phenolic glycolipid 1 (PGL-1) with myelinating glia their subsequent infection. Here, we use transparent zebrafish larvae visualize earliest events leprae-induced nerve damage. We find that axonal damage are not directly initiated by but infected macrophages...
Type I interferon (IFN) alpha/beta is critical for host defense. During endotoxicosis or highly lethal bacterial infections where systemic inflammation predominates, mice deficient in IFN-alpha/beta receptor (IFNAR) display decreased and improved outcome. However, human sepsis mortality often occurs during a prolonged period of immunosuppression not from exaggerated inflammation. We used low lethality cecal ligation puncture (CLP) model to determine the role type IFNs defense sepsis. Despite...
Abstract Bone marrow (BM) hematopoietic stem and progenitor cells (HSPCs) can be activated by type I IFNs, TLR agonists, viruses, bacteria to increase hematopoiesis. In this study, we report that endotoxin treatment in vivo induces TLR4, MyD88, Toll/IL-1 resistance domain-containing adaptor-inducing IFN-β (TRIF)-dependent expansion of BM HSPCs. Bacterial infection Staphylococcus aureus or cecal ligation puncture also HSPC expansion, but TRIF, IFN, cytokine, PG, oxidative stress pathways are...
Successful host defense against pathogens requires innate immune recognition of the correct pathogen associated molecular patterns (PAMPs) by receptors (PRRs) to trigger appropriate gene program tailored pathogen. While many PRR pathways contribute response specific pathogens, relative importance each pathway for complete transcriptional elicited has not been examined in detail. Herein, we used RNA-sequencing with wildtype and mutant macrophages delineate contributing early Staphylococcus...
Triggering antimicrobial mechanisms in macrophages infected with intracellular pathogens, such as mycobacteria, is critical to host defense against the infection. To uncover unique and shared networks induced by innate adaptive immune systems, gene expression profiles generated RNA sequencing (RNAseq) from human monocyte-derived (MDMs) activated TLR2/1 ligand (TLR2/1L) or IFN-γ were analyzed. Weighed correlation network analysis identified modules of genes strongly correlated TLR2/1L that...
Abstract The cecum contains a high concentration of microbes, which are combination Gram‐negative and Gram‐positive flora. These bacteria range from anaerobic to facultative aerobic organisms. In the procedure described in this unit, ligation produces source ischemic tissue as well polymicrobial infection. This ischemic/necrotic microbial infection distinguishes multifactorial model number other bacterial sepsis models, including but not limited to: bacteremia secondary intravenous or...
Abstract Cancer progression is associated with inflammation, increased metabolic demand, infection, cachexia, and eventually death. Myeloid-derived suppressor cells (MDSCs) commonly expand during cancer are adaptive immune suppression inflammatory metabolite production. We propose that cancer-induced cachexia driven at least in part by the expansion of MDSCs. MDSC 4T1 mammary carcinoma-bearing hosts induction a hepatic acute-phase protein response altered host energy fat metabolism, reduced...
Intraperitoneal exposure of nonautoimmune mice to 2,6,10,14-tetramethylpentadecane (TMPD) causes lupus and the formation ectopic lymphoid tissue. Although associated with humoral autoimmunity, it is not known whether Ab responses develop within tissue or if B cells only secondarily migrate there. We show that induced by TMPD resembles secondary morphologically, but also displays characteristics germinal center reactions. Proliferating T lymphocytes were found tissue, activation-induced...
ABSTRACT Previous studies have suggested that neonates rely heavily on innate immunity for their antimicrobial response to bacterial infections. However, the immune by infection remains poorly characterized. Here, we show in a murine model of neonatal polymicrobial sepsis, CXC ligand 10 (CXCL10) concentrations increase blood and peritoneum concordant with peritoneal recruitment granulocytes macrophages. Additionally, receptor 3 (CXCR3) expression elicited macrophages increases following...
New vaccine platforms that activate humoral immunity and generate neutralizing antibodies are required to combat emerging pathogens, including influenza virus. A slurry of antigen-loaded hydrogel microparticles anneal form a porous scaffold with high surface area for antigen uptake by infiltrating immune cells as the biomaterial degrades is demonstrated enhance immunity. Antigen-loaded-microgels elicited robust cellular response, increased CD4
Current evidence suggests that neonatal immunity is functionally distinct from adults. Although TLR signaling through the adaptor protein, MyD88, has been shown to be critical for survival sepsis in adults, little known about role of MyD88 or TRIF sepsis. We demonstrate TRIF(-/-) but not MyD88(-/-) neonates are highly susceptible Escherichia coli peritonitis and bacteremia. This was associated with decreased innate immune recruitment function. Importantly, we found reverse true adults...
Classic Ehlers-Danlos syndrome (cEDS) is a genetic disorder of the connective tissue that characterized by mutations in genes coding type V collagen. Wound healing defects are characteristic cEDS and no therapeutic strategies exist. Herein we describe murine model phenocopies wound seen humans. Our features mice with conditional loss