A5027079588- Reproductive tract infections research
- SARS-CoV-2 and COVID-19 Research
- Reproductive System and Pregnancy
- COVID-19 Clinical Research Studies
- Mosquito-borne diseases and control
- HIV Research and Treatment
- Viral Infections and Vectors
- interferon and immune responses
- Adolescent Sexual and Reproductive Health
- Cervical Cancer and HPV Research
- Urinary Tract Infections Management
- Respiratory viral infections research
- Genital Health and Disease
- Viral Infections and Outbreaks Research
- Clostridium difficile and Clostridium perfringens research
- Single-cell and spatial transcriptomics
- Autophagy in Disease and Therapy
- Syphilis Diagnosis and Treatment
- HIV/AIDS Research and Interventions
- SARS-CoV-2 detection and testing
- Urinary and Genital Oncology Studies
- Animal Disease Management and Epidemiology
- Vector-Borne Animal Diseases
- Virology and Viral Diseases
- Inflammasome and immune disorders
National Institutes of Health
2011-2024
National Institute of Allergy and Infectious Diseases
2013-2024
Institute of Cellular and Intracellular Symbiosis
2008
Single-cell RNA sequencing of lungs SARS-CoV-2–infected African green monkeys reveals virus replication and host response dynamics in vivo.
ABSTRACT Chlamydia trachomatis causes chronic inflammatory diseases of the eye and genital tract has global medical importance. The chlamydial plasmid plays an important role in pathophysiology these diseases, as plasmid-deficient organisms are highly attenuated. cryptic carries noncoding RNAs eight conserved open reading frames (ORFs). To understand gene function, we generated shuttle vectors with deletions each ORFs. individual deletion mutants were used to transform chlamydiae...
Blinding trachoma is an ancient neglected tropical disease caused by Chlamydia trachomatis for which a vaccine needed. We describe live-attenuated that safe and efficacious in preventing nonhuman primates, model with excellent predictive value humans. Cynomolgus macaques infected ocularly strain deficient the 7.5-kb conserved plasmid presented short-lived infections resolved spontaneously without ocular pathology. Multiple attenuated plasmid-deficient produced no inflammatory pathology but...
Chlamydia trachomatis is a human pathogen associated with significant morbidity worldwide. As obligate intracellular parasites, chlamydiae must survive within eukaryotic cells for sufficient time to complete their developmental cycle. To promote host cell survival, express poorly understood anti-apoptotic factors. Using recently developed genetic tools, we show that three inclusion membrane proteins (Incs) out of eleven examined are required stability and avoidance death pathways. In the...
Tripartite motif-containing protein 5α (TRIM5α) is a cellular antiviral restriction factor that prevents early events in retrovirus replication. The activity of TRIM5α thought to be limited retroviruses as result highly specific interactions with capsid lattices. In contrast this current understanding, we show both human and rhesus macaque suppress replication flaviviruses. Multiple viruses the tick-borne encephalitis complex are sensitive TRIM5α-dependent restriction, but mosquito-borne...
Inflammation in response to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection drives severity of coronavirus disease 2019 (COVID-19) and is influenced by host genetics. To understand mechanisms inflammation, animal models that reflect genetic diversity clinical outcomes observed humans are needed. We report a mouse panel comprising the genetically diverse Collaborative Cross (CC) founder strains crossed human ACE2 transgenic mice (K18-hACE2) confers susceptibility...
ABSTRACT Chlamydia trachomatis is a globally important obligate intracellular bacterial pathogen that leading cause of sexually transmitted disease and blinding trachoma. Effective control these diseases will likely require preventative vaccine. C. polymorphic membrane protein D (PmpD) an attractive vaccine candidate as it conserved among strains target broadly cross-reactive neutralizing antibodies. We show here immunoaffinity-purified native PmpD exists oligomer with distinct 23-nm...
Chlamydia trachomatis is a human pathogen of global importance. An obstacle to studying the pathophysiology chlamydial disease lack suitable murine model C. infection. Mice are less susceptible infection with isolates due in part innate mouse-specific host defense mechanisms which strains sensitive. Another possible factor that influences susceptibility mice commonly cultivated vitro prior mice; therefore, virulence genes could be lost as consequence negative selective pressure. We tested...
Chlamydia muridarum and trachomatis, mouse human strains, respectively, have been used to study immunity in a murine model of female genital tract infection. Despite evidence that unique genes these otherwise genomically similar strains could play role innate immune evasion their respective hosts, there no animal findings directly support this conclusion. Here, we infected C57BL/6 adaptive immune-deficient Rag1(-/-) mice with evaluated ability spontaneously resolve Predictably, cleared...
Abstract Chlamydia trachomatis infection causes severe inflammatory disease resulting in blindness and infertility. The pathophysiology of these diseases remains elusive but myeloid cell-associated inflammation has been implicated. Here we show NLRP3 inflammasome activation is essential for driving a macrophage-associated endometritis infertility by using female mouse genital tract chlamydial model. We find the parasitophorous vacuole protein CT135 triggers via TLR2/MyD88 signaling as...
Dysregulated inflammation dominated by chemokine expression is a key feature of disease following infection with the globally important human pathogens Zika virus (ZIKV) and dengue virus, but mechanistic understanding how pro-inflammatory responses are initiated lacking. Mitophagy quality-control mechanism that regulates innate immune signaling cytokine production through selective degradation damaged mitochondria. Here, we demonstrate ZIKV nonstructural protein 5 (NS5) antagonizes mitophagy...
Advanced age is a key predictor of severe COVID-19. To gain insight into this relationship, we used the rhesus macaque model SARS-CoV-2 infection. Eight older and eight younger macaques were inoculated with SARS-CoV-2. Animals evaluated using viral RNA quantification, clinical observations, thoracic radiographs, single-cell transcriptomics, multiparameter flow cytometry, multiplex immunohistochemistry, cytokine detection, lipidomics analysis at predefined time points in various tissues....
Chlamydia trachomatis is an obligate intracellular epitheliotropic bacterial pathogen of humans. Infection the eye can result in trachoma, leading cause preventable blindness world. The pathophysiology blinding trachoma driven by multiple episodes reinfection conjunctival epithelial cells, producing intense chronic inflammatory response resulting submucosal tissue remodeling and scarring. Recent reports have shown that infection with organisms lacking cryptic chlamydial plasmid highly...
Abstract Trachoma, caused by the obligate intracellular organism Chlamydia trachomatis, is world’s leading cause of preventable blindness for which a vaccine needed. We have previously shown that plasmid-deficient live-attenuated trachoma delivered ocularly to macaques elicited either solid or partial protective immunity against virulent ocular challenge. Solidly protected shared same MHC class II alleles implicating CD4+ T cells in superior immunity. Understandably, we sought define cell...
Chlamydia trachomatis is an obligate intracellular bacterium that a globally important human pathogen. The chlamydial plasmid attenuating virulence factor, but the molecular basis for attenuation not understood. Chlamydiae replicate within membrane-bound vacuole termed inclusion, where they undergo biphasic developmental growth cycle and differentiate from noninfectious into infectious organisms. Late in cycle, fragile chlamydia-laden inclusion retains its integrity by surrounding itself...
Chlamydia muridarum and trachomatis mouse models of genital infection have been used to study chlamydial immunity vaccine development. To assess the protective role CD4(+) T cells in resolving C. tract infections, we female model evaluated presence absence cells. In contrast infection, was unaltered Mice infected with developed re-challenge, but unlike optimum resistance required multiple infectious challenges, despite generation adaptive serum local specific immune responses. Thus,...
Chlamydia trachomatis is an obligate intracellular mucosotropic pathogen of significant medical importance. It the etiological agent blinding trachoma and bacterial sexually transmitted diseases, infections that afflict hundreds millions people globally. The C. polymorphic membrane protein D (PmpD) a highly conserved autotransporter target broadly cross-reactive neutralizing antibodies; however, its role in host-pathogen interactions unknown. Here we employed targeted reverse genetics...
The yellow fever virus 17D (YFV-17D) live attenuated vaccine is considered one of the most successful vaccines ever generated associated with high antiviral immunity, yet signaling mechanisms that drive response in infected cells are not understood. Here, we provide a molecular understanding how metabolic stress and innate immune responses linked to type I IFN expression YFV-17D infection. Comparison replication its parental virus, YFV-Asibi, related dengue revealed requires RIG-I-like...
Background Sexually transmitted infections (STIs) are associated with an increased risk of HIV infection. To model the interaction between STIs and infection, we evaluated capacity pigtail macaque to sustain triple infection Trichomonas vaginalis, Chlamydia trachomatis, SHIVSF162P3. Methods Seven SHIVSF162P3-infected macaques were inoculated T. vaginalis only (n = 2), C. trachomatis 1), both or control media (no STI; n 2). Infections confirmed by culture and/or nucleic acid testing. Genital...
Background. Sexually transmitted infections (STIs) are associated with an increased risk of human immunodeficiency virus (HIV) infection, but their biological effect on HIV susceptibility is not fully understood.
Chlamydia trachomatis and C. muridarum are human mouse pathogens, respectively, which show high conservation of gene order content. Both species contain a common 7.5-kb plasmid that is an important virulence factor. Recently described transformation systems have been used to characterize L2 functions; however, similar studies not reported for ocular tropic serovar A or the strain, muridarum. Here, we conducted genetic experiments with report following: (1) successful restricted shuttle...
The unprecedented 2013–2016 outbreak of Ebola virus (EBOV) resulted in over 11,300 human deaths. Host resistance to RNA viruses requires RIG-I-like receptor (RLR) signaling through the adaptor protein, mitochondrial antiviral protein (MAVS), but role RLR-MAVS orchestrating anti-EBOV responses vivo is not known. Here we apply a systems approach MAVS−/− mice infected with either wild-type or mouse-adapted EBOV. MAVS controlled EBOV replication expression IFNα, regulation inflammatory spleen,...
Chlamydiae are widespread Gram-negative pathogens of humans and animals. Salicylidene acylhydrazides, developed as inhibitors type III secretion system (T3SS) in Yersinia spp., have an inhibitory effect on chlamydial infection. However, these also the capacity to chelate iron, it is possible that their antichlamydial effects caused by iron starvation. Therefore, we explored modification salicylidene acylhydrazides with goal uncouple from We discovered benzylidene which cannot inhibit growth....
Chlamydia trachomatis is an important human pathogen causing both ocular and sexually transmitted disease. Recently, we identified CT135 as virulence determinant in a mouse infection model. Results from CEL 1 digestion assays sequencing analyses indicated that was much more polymorphic high vitro passage reference serovars than it clinical strains had undergone limited passaging. Herein, used targeted next-generation of the CT134-135 locus, isolates, enabling accurate discovery single...