A5018165248- Reproductive tract infections research
- Immune Response and Inflammation
- Reproductive System and Pregnancy
- interferon and immune responses
- Pelvic floor disorders treatments
- Advanced Glycation End Products research
- Inflammasome and immune disorders
- Reproductive Physiology in Livestock
- Cytokine Signaling Pathways and Interactions
- Immune Cell Function and Interaction
- Eicosanoids and Hypertension Pharmacology
- Calcium signaling and nucleotide metabolism
- Sleep and Work-Related Fatigue
- Antimicrobial Peptides and Activities
- International Law and Human Rights
- Cancer, Hypoxia, and Metabolism
- Reproductive Health and Contraception
- Urinary Tract Infections Management
- NF-κB Signaling Pathways
- European and International Law Studies
- Cancer-related molecular mechanisms research
- Immune cells in cancer
- Genital Health and Disease
- Fatty Acid Research and Health
- Viral Infections and Vectors
University of Maryland, Baltimore
2012-2024
University of Arkansas for Medical Sciences
2008-2012
Arkansas Children's Hospital
2011-2012
Abstract IFN-β has been implicated as an effector of oviduct pathology resulting from genital chlamydial infection in the mouse model. In this study, we investigated role cytosolic DNA and engagement sensors expression during infection. We determined that three-prime repair exonuclease-1, a host 3′ to 5′ exonuclease, reduced significantly using small interfering RNA gene knockout fibroblasts, implicating ligand for response. The sensor cyclic GMP–AMP synthase (cGAS) shown bind generate...
Type I IFN signaling has recently been shown to be detrimental the host during infection with Chlamydia muridarum in both mouse lung and female genital tract. However, pattern recognition receptor pathways involved chlamydial-induced IFN-beta are unclear. Previous studies have demonstrated no role for TLR4 a partial MyD88 IFN-beta. In this study, we demonstrate that macrophages lacking TLR3, TRIF, TLR7, or TLR9 individually MyD88, still induce equivalent wild type controls, leading...
ABSTRACT Type I interferons (IFNs) induced during in vitro chlamydial infection exert bactericidal and immunomodulatory functions. To determine the precise role of type IFNs vivo genital infection, we examined course outcome Chlamydia muridarum mice genetically deficient receptor for (IFNAR −/− mice). A significant reduction shedding duration lower tract was observed IFNAR comparison to level wild-type (WT) mice. Furthermore, developed less chronic oviduct pathology that WT Compared WT, had...
Recent findings have implicated interleukin-1beta (IL-1beta) as an important mediator of the inflammatory response in female genital tract during chlamydial infection. But how IL-1beta is produced and its specific role infection pathology are unclear. Therefore, our goal was to determine functional consequences cellular sources expression a In present study, IL-1beta(-/-) mice exhibited delayed clearance decreased frequency hydrosalpinx compared wild-type (WT) mice, implying for both...
Abstract IL-1β has been implicated in the development of oviduct pathology during Chlamydia muridarum genital infection mouse model. The goal this study was to characterize role IL-1 signaling and inflammasome-activation pathways chlamydial infection. Compared with control mice, IL-1R–deficient mice displayed delayed clearance increased colonization. Consistent for clearance, deficient IL-1R antagonist cleared at a faster rate. Despite infection, had significantly reduced pathology, which...
We have previously shown that MyD88 knockout (KO) mice exhibit delayed clearance of Chlamydia muridarum genital infection compared to wild-type (WT) mice. A blunted Th1 response and ineffective suppression the Th2 were also observed in KO The goal present study was investigate specific mechanisms whereby absence leads these effects address compensatory tract ultimately clear MyD88. It NK cells recruited failed produce gamma interferon (IFN-γ) mRNA protein. This defect associated with...
Abstract The highly reactive compound methylglyoxal (MG) can cause direct damage to cells and tissues by reacting with cellular macromolecules. MG has been identified as a biomarker associated increased sepsis-induced mortality. Patients undergoing septic shock have significantly elevated circulating levels compared postoperative patients healthy controls. Furthermore, implicated in the development of type II diabetes mellitus Alzheimer’s disease. Because is generated during glycolysis, we...
Two cosegregating single-nucleotide polymorphisms (SNPs) in human TLR4, an A896G transition at SNP rs4986790 (D299G) and a C1196T rs4986791 (T399I), have been associated with LPS hyporesponsiveness differential susceptibility to many infectious or inflammatory diseases. However, studies failed confirm these associations, transfection experiments resulted conflicting conclusions about the impact of SNPs on TLR4 signaling. Using advanced protein modeling from crystallographic data murine we...
Mice with the type I interferon (IFN) receptor gene knocked out (IFNAR KO mice) or deficient for alpha/beta IFN (IFN-α/β) signaling clear chlamydial infection earlier than control mice and develop less oviduct pathology. Initiation of host IFN-β transcription during an in vitro requires regulatory factor 3 (IRF3). The goal present study was to characterize influence IRF3 on genital its relationship expression mouse model. were able resolve as well mice, overcoming increased colonization...
In many important human pathogens, such as Shigella and Salmonella spp., the bacterial type III secretion (T3S) apparatus is required to initiate inflammation via activation of caspase-1- or NF-kappaB-dependent genes. Using an ex vivo infection model, goal present study was determine whether chlamydial T3S also modulates host inflammatory response. Infections mouse peritoneal macrophages were performed with Chlamydia muridarum, expression cytokines monitored by quantitative reverse...
Resolution of Chlamydia genital tract infection is delayed in the absence MyD88. In these studies, we first used bone marrow chimeras to demonstrate a requirement for MyD88 expression by hematopoietic cells presence wild-type epithelium. Using mixed then determined that was specifically required adaptive immune compartment. Furthermore, adoptive transfer experiments revealed CD4(+) T cell necessary normal resolution infection. This associated with reduced ability MyD88(-/-)CD4(+) accumulate...
Despite widespread use of annual influenza vaccines, seasonal influenza-associated deaths number in the thousands each year, part because exacerbating bacterial superinfections. Therefore, discovering additional therapeutic options would be a valuable aid to public health. Recently, TLR4 inhibition has emerged as possible mechanism for protection against lethality and acute lung injury. Based on recent data showing that rhesus macaque θ-defensins could inhibit TLR4-dependent gene expression,...
Inflammatory bowel disease (IBD), including Crohn's and ulcerative colitis, impacts millions of individuals worldwide severely impairs the quality life for patients. Dysregulation innate immune signaling pathways reduces barrier function exacerbates progression. Macrophage (Mφ) are potential targets IBD therapies. While multiple treatments available IBD, (i) not all patients respond, (ii) responses may diminish over time, (iii) often have undesirable side effects. Genetic studies shown that...
Abstract Approximately one million cases of sepsis in the U.S.A. occur annually. The early phase features dramatic changes host metabolism and inflammation. While examining effects metabolic pathways on inflammation, we discovered that highly reactive glycolytic metabolite, methylglyoxal (MG), accumulates intracellularly during classical activation macrophages. Herein, explored role glycolysis master regulator glycolysis, Hypoxia-Inducing Factor-1α (HIF-1α), inflammation MG accumulation...
Abstract The host protein STING has been shown to be essential for recognition of both viral and intracellular bacterial pathogens, but its regulation remains unclear. Previously, we have described how mitochondrial membrane potential regulates STING-dependent IFN-β induction. kinase activity AMPK is controlled by cellular metabolism calcium concentration. goal our study was examine whether signaling regulated AMPK. Addition an chelator or inhibitor suppressed induction in mouse macrophages...
The type III secretion (T3S) apparatus is a virulence factor in many gram negative bacteria such as Pseudomonas spp., Salmonella and Chlamydia spp. Depending on the bacterial species, T3S has been shown to initiate inflammation or inhibit cytokine production. goal of present study was determine how chlamydial modulates host inflammatory response. Since there no genetic system for blockade accomplished pharmacologically. Infections murine peritoneal macrophages were performed using mouse...
Abstract IL-1β has been implicated in the development of oviduct pathology during Chlamydia muridarum genital infection mouse model. The goal this study was to characterize role IL-1 signaling and inflammasome activation pathways C. infection. Compared control mice, receptor KO (knockout) mice display delayed clearance increased burden, but very few incidences hydrosalpinx. Consistent with observation, IL-1R antagonist an opposite phenotype rapid clearance. Flow cytometry analysis at day 10...
Abstract Recent findings have implicated secretion of the proinflammatory cytokine interleukin-1β as a crucial player in female genital tract pathology during chlamydial infection. However, major cellular source IL-1β an vivo infection and mechanistic details its release yet to be determined. In present study, flow cytometry was used isolate highly enriched cell populations from tracts C. muridarum infected mice at peak secretion. Purified F4/80+ macrophages Ly-6G+ neutrophils, but not CD45-...
Abstract We have previously shown that MyD88-/- mice delayed clearance of C. muridarum genital infection in comparison to wild type (WT) mice. The goal the present study was investigate specific mechanisms by which MyD88 protects against C.muridarum infection. A 10-fold higher bacterial load observed cervical tissues at day (d) 4-post infection, suggesting impairment early innate response. Further, IFNγ levels were undetectable secretions until d4-d5 post though they restored normal d7...