A5016179033- Reproductive tract infections research
- Reproductive System and Pregnancy
- Immune Cell Function and Interaction
- Immune Response and Inflammation
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Bacillus and Francisella bacterial research
- Gut microbiota and health
- Escherichia coli research studies
- Urinary Tract Infections Management
- Bacteriophages and microbial interactions
- Reproductive Physiology in Livestock
- Viral gastroenteritis research and epidemiology
- Cervical Cancer and HPV Research
- Bacterial Genetics and Biotechnology
- Clostridium difficile and Clostridium perfringens research
- Toxin Mechanisms and Immunotoxins
- Antimicrobial Peptides and Activities
- Vibrio bacteria research studies
- Yersinia bacterium, plague, ectoparasites research
- Listeria monocytogenes in Food Safety
- Viral Infections and Outbreaks Research
- Cellular transport and secretion
- Salmonella and Campylobacter epidemiology
- Genital Health and Disease
Harvard University
2014-2025
Moscow Research and Clinical Center for Neuropsychiatry
2021
Laboratory of Molecular Genetics
2008
Corixa Corporation
2001
University of Washington
1994-2001
Howard Hughes Medical Institute
1994-1995
Stanford University
1988-1992
Genital Chlamydia trachomatis (Ct) infection induces protective immunity that depends on interferon-γ-producing CD4 T cells. By contrast, we report mucosal exposure to ultraviolet light (UV)-inactivated Ct (UV-Ct) generated regulatory cells exacerbated subsequent infection. We show immunization with UV-Ct complexed charge-switching synthetic adjuvant particles (cSAPs) elicited long-lived protection in conventional and humanized mice. UV-Ct-cSAP targeted immunogenic uterine CD11b(+)CD103(-)...
Summary Salmonella typhimurium grown under oxygen‐limiting conditions were found to enter into, elicit actin filament rearrangement in, and effect morphological changes upon HEp‐2 cells within 15 min after infection. Video microscopy revealed that host cell associated with entry began 1 of productive adherence. Polarized Caco‐2 morphology was affected 40 s infection low‐oxygen‐grown S. typhimurium. Stationary‐phase did not these phenomena this time‐period even when adherence enhanced the...
Summary Surface protein mutants of the invasive Salmonella species, S. choleraesuis , were generated using transposon TnphoA. 626 alkaline phosphatase (PhoA + ) fusion identified and screened for their ability to pass through (transcytose) polarized epithelial monolayers Madin Darby canine kidney (MDCK) cells grown on membrane filters. Forty two unable this barrier. All these transcytosis adhere or invade MDCK monolayers, yet mutations not in genes encoding type 1 pili mannose‐resistant...
Chlamydia trachomatis infection is the most common bacterial sexually transmitted disease in United States. infections that ascend to upper genital tract can persist, trigger inflammation, and result serious sequelae such as infertility. However, mouse models which vaginal vault inoculated with C. do not recapitulate course of human disease. These intravaginal efficiently tract, cause persistent infection, induce significant CD4⁺ T cell infiltration. In this article, we describe a...
A sensitive detection system specific for Legionella pneumophila in water was developed. This is based on amplification of a chromosomal DNA sequence from L. by the polymerase chain reaction, followed amplified product hybridization radiolabeled oligodeoxynucleotide. After 35 cycles amplification, sample which had been seeded with CFU contained sufficient to be detected dot blots. Bacteria other genera tested did not generate positive signals under these conditions. Application this...
Chlamydia trachomatis is an obligate intracellular bacterium that causes a variety of diseases in humans. C. has complex developmental cycle depends on host cells for replication, during which gene expression tightly regulated. Here we identify two proteases possess deubiquitinating and deneddylating activities. We have designated these proteins ChlaDub1 ChlaDub2. The genes encoding ChlaDub2 are present all species except pneumoniae, their catalytic domains bear similarity to the other...
In order to better understand the regulation of Pseudomonas aeruginosa flagellin expression we cloned sigma factor RNA polymerase used transcribe gene. It is a member 28 class alternative factors described in several bacterial genera. Using published sequence fliA gene encoding from Salmonella typhimurium, designed two oligonucleotides and, using chain reaction, isolated S. typhimurium chromosomal DNA. This heterologous probe was DNA blot analysis restriction digests P. A 1.7 kb SalI-EcoRI...
Abstract T cell responses are often an important component in immunity to organisms that replicate intracellularly. Cytotoxic lymphocyte (CTL) recognition of peptide Ag the context MHC class I molecules results lysis infected cells and release cytokines including IFN-gamma. Members genus Chlamydia obligate intracellular pathogens cause blindness sexually transmitted disease worldwide. Even though it replicates within a membrane-bound vacuole, trachomatis may elicit CTL response if Ags...
Abstract Chlamydiae are obligate intracellular bacterial pathogens that exhibit a broad range of host tropism. Differences in tropism between Chlamydia species have been linked to variations IFN-γ-mediated immune responses. In mouse cells, IFN-γ can effectively restrict growth the human pathogen trachomatis but fails control closely related muridarum. The ability cells resist C. replication is largely dependent on induction family IFN-γ-inducible GTPases called immunity-related or IRGs. this...
The presence of a complex and diverse intestinal flora is functionally important for regulating mucosal immune responses. However, the extent to which balanced regulates systemic responses still being defined. In order specifically examine whether acquisition less influences immunization in pre-weaning stages life, we utilize model infant mice acquire an from their mothers that has been altered by broad-spectrum antibiotics. this model, pregnant dams are treated with cocktail antibiotics...
During infection with Chlamydia trachomatis , CD8 + T cells are primed, even though the bacteria remain confined to a host cell vacuole throughout their developmental cycle. Because recognize antigens processed from cytosolic proteins, recognized by these very likely have access cytoplasm during infection. The identity of C. proteins has remained elusive, localization suggests they may play important roles in biology organism. Here we use retroviral expression system identify Cap1, 31-kDa...
The protective antigen (PA) component of anthrax toxin mediates entry the toxin's lethal factor (LF) and edema into cytosolic compartment mammalian cells. amino-terminal domain LF (LFn; 255 amino acids) binds to PA, when fused heterologous proteins, LFn delivers such proteins cytoplasm in presence PA. In current study, we a 9-amino acid cytotoxic T-lymphocyte (CTL) epitope (LLO91-99) from an intracellular pathogen, Listeria monocytogenes, measured ability resulting LFn-LLO91-99 fusion...
Abstract Dendritic cells provide a critical link between innate and acquired immunity. In this study, we demonstrate that the bacterial pathogen Salmonella enterica serovar Typhimurium can efficiently kill these professional phagocytes via mechanism is dependent on sipB pathogenicity island 1-encoded type III protein secretion system. Rapid phosphatidylserine redistribution, caspase activation, loss of plasma membrane integrity were characteristic dendritic infected with wild-type...
Abstract During its developmental cycle, the intracellular bacterial pathogen Chlamydia trachomatis remains confined within a protective vacuole known as an inclusion. Nevertheless, CD8+ T cells that recognize Ags in context of MHC class I molecules are primed during infection. I-restricted presentation these suggests proteins or domains from them have access to host cell cytoplasm. products with cytoplasm define subset uniquely positioned interface environment pathogen’s cycle. In addition...
ABSTRACT In this study, we used mice in which the gene for gamma interferon (IFN-γ) has been disrupted (IFN-γ −/− mice) to study role of cytokine resolution Chlamydia trachomatis infection. We show that IFN-γ are impaired ability clear infection with C. compared +/+ control mice. Activated CD8 + cytotoxic T lymphocytes (CTL) secrete response intracellular infection, and have shown previously a -specific CTL line can reduce when adoptively transferred into infected present found these lines...
Numerous bacterial pathogens manipulate host cell processes to promote infection and ultimately cause disease through the action of proteins that they directly inject into cells. Identification targets molecular mechanisms used by these effector is critical understanding pathogenesis. We have developed a systems biological approach using yeast Saccharomyces cerevisiae can expedite identification cellular targeted proteins. systematically screened viable haploid deletion strain collection for...
Infections caused by the bacteria Chlamydia trachomatis contribute to diverse pathologies in a variety of human populations. We previously used systemic model C. infection mice map three quantitative trait loci that influence vivo susceptibility differences between C57BL/6J and C3H/HeJ inbred strains mouse. One these loci, Ctrq-3, influences an IFN-gamma-dependent difference primary embryonic fibroblasts isolated from strains. Here we use fine structure mapping congenic carrying DNA...
Infection with the obligate intracellular bacterium Chlamydia trachomatis is controlled primarily by IFN-gamma and Th1 immunity. In this study, we used cells from a Chlamydia-specific CD4(+) TCR-transgenic mouse to assess role of in development We show that secretion host or ability respond secreted not required initiate immune response. Additionally, found Ag-specific were preskewed toward confer protection, whereas Th2 cause previously unreported exacerbation disease leading higher...
Abstract The immunity-related GTPases (IRG), also known as p47 GTPases, are a family of proteins that tightly regulated by IFNs at the transcriptional level and serve key mediators IFN-regulated resistance to intracellular bacteria protozoa. Among IRG proteins, loss Irgm1 has most profound impact on IFN-γ-induced host physiological level. Surprisingly, losses seen in absence sometimes more striking than those IFN-γ. In current work, we address underlying mechanism. We find several contexts,...