Chlamydia trachomatis is the most commonly reported agent of sexually transmitted bacterial infec... more Chlamydia trachomatis is the most commonly reported agent of sexually transmitted bacterial infections worldwide. This pathogen frequently leads to persistent, long-term, subclinical infections, which in turn may cause severe pathology in susceptible hosts. This is in part due to the strategies that Chlamydia trachomatis uses to survive within epithelial cells and to evade the host immune response, such as subverting intracellular trafficking, interfering signaling pathways and preventing apoptosis. Innate immune receptors such as toll-like receptors expressed on epithelial and immune cells in the genital tract mediate the recognition of chlamydial molecular patterns. After bacterial recognition, a subset of pro-inflammatory cytokines and chemokines are continuously released by epithelial cells. The innate immune response is followed by the initiation of the adaptive response against Chlamydia trachomatis, which in turn may result in T helper 1-mediated protection or in T helper 2-m...
OBJECTIVE Detecting traces of ancient DNA of Vibrio cholerae to provide genetic information assoc... more OBJECTIVE Detecting traces of ancient DNA of Vibrio cholerae to provide genetic information associated with the fifth cholera pandemic. MATERIALS Sediment samples from the sacral foramina of four individuals were analyzed, recovered from a mass grave near an institution dedicated exclusively to the isolation and treatment of citizens infected with cholera in the late 19th century in the city of Cordoba, Argentina. METHODS Paleogenetic techniques (ancient DNA extraction, PCR amplification, and Sanger sequencing) were applied. Specific primers for Vibrio cholerae (VCR, ctxA, ctxB, and tcpA) were designed. RESULTS By amplifying and sequencing the Vibrio cholerae repeats fragment, the infection in at least one individual was confirmed. CONCLUSIONS The synthesis of the paleogenetic results with the archaeological and historical evidence strongly supports that at least one individual from the mass grave in Cordoba, Argentina, was a victim of the fifth cholera pandemic. SIGNIFICANCE Confirming the presence of the disease through multiple lines of evidence, including genetic, archaeological, and historical analyses, strengthens and affirms our understanding of the presence, effects, and potential evolutionary paths of the disease in the past. LIMITATIONS Vibrio cholerae repeats were sequenced in one individual, while the remaining genes could not be amplified, which is likely related to gene copy number. SUGGESTIONS FOR FUTURE RESEARCH Paleogenetic examination of ancient samples from different locations will broaden our understanding of the origin, evolution, and past dissemination of Vibrio cholerae epidemic strains.
Annual Review of Cell and Developmental Biology, Nov 10, 2012
Lipid droplets (LDs) are neutral lipid storage organelles ubiquitous to eukaryotic cells. It is i... more Lipid droplets (LDs) are neutral lipid storage organelles ubiquitous to eukaryotic cells. It is increasingly recognized that LDs interact extensively with other organelles and that they perform functions beyond passive lipid storage and lipid homeostasis. One emerging function for LDs is the coordination of immune responses, as these organelles participate in the generation of prostaglandins and leukotrienes, which are important inflammation mediators. Similarly, LDs are also beginning to be recognized as playing a role in interferon responses and in antigen cross presentation. Not surprisingly, there is emerging evidence that many pathogens, including hepatitis C and Dengue viruses, Chlamydia, and Mycobacterium, target LDs during infection either for nutritional purposes or as part of an anti-immunity strategy. We here review recent findings that link LDs to the regulation and execution of immune responses in the context of host-pathogen interactions.
IntroductionInfection with Human Papillomavirus (HPV) is a recognized risk factor for Chlamydia t... more IntroductionInfection with Human Papillomavirus (HPV) is a recognized risk factor for Chlamydia trachomatis (CT) infection and vice versa. Coinfection of HPV and CT in women is a very common and usually asymptomatic finding that has been linked to increased risk of cervical cancer. It has been demonstrated that CT facilitates the entry of multiple high risk HPV genotypes, leading to damage of the mucosal barrier and interfering with immune responses and viral clearance, which ultimately favours viral persistence and malignant transformation. Although the facilitating effects elicited by CT infection on viral persistence have been reported, little is known about the consequences of HPV infection on CT development.MethodsHerein, we took advantage of a genetically modified human cervical cell line co-expressing HPV-16 major oncogenic proteins E6 and E7, as an experimental model allowing to investigate the possible effects that HPV infection would have on CT development.Results and disc...
Chlamydia trachomatis is an obligate intracellular pathogen and the leading bacterial cause of se... more Chlamydia trachomatis is an obligate intracellular pathogen and the leading bacterial cause of sexually transmitted infections worldwide. Chlamydia trachomatis genovars L1–L3 are responsible for lymphogranuloma venereum (LGV), an invasive sexually transmitted disease endemic in tropical and subtropical regions of Africa, South America, the Caribbean, India and South East Asia. The typical signs and symptoms of C. trachomatis LGV urogenital infections in men include herpetiform ulcers, inguinal buboes, and/or lymphadenopathies. Since 2003, endemic cases of proctitis and proctocolitis caused by C. trachomatis LGV emerged in Europe, mainly in HIV-positive men who have sex with men (MSM). Scarce data have been reported about unusual clinical presentations of C. trachomatis LGV urogenital infections. Herein, we report a case of a 36-year-old heterosexual, HIV-negative male declaring he did not have sex with men or trans women, who presented to the Urology and Andrology outpatient clinic ...
a<p>The predicted stem-loop structures and origin of these small RNAs is depicted in <a ... more a<p>The predicted stem-loop structures and origin of these small RNAs is depicted in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0106434#pone.0106434.s004" target="_blank">Fig. S4</a>.</p><p>Top 10 small RNA reads of <i>M. smegmatis</i>.</p
<p>(<b>A</b>) Wildtype MEFs were treated overnight with OA and IFNγ and immunos... more <p>(<b>A</b>) Wildtype MEFs were treated overnight with OA and IFNγ and immunostained for endogenous Irgm3 and for LDs using BODIPY. (<b>B</b>) Wildtype MEFs were transfected with the three mouse paralogs Irgm1-3 tagged with V5, infected with <i>C. trachomatis</i> and treated with OA and IFNγ at 3 hpi. Cells were fixed at 20 hpi and stained with anti-V5, BODIPY and Hoechst. White arrows point at inclusions. (<b>C</b>) The localization of the GKS proteins Irga6 and Irgb6 were visualized in wildtype and <i>Irgm1/m3<sup>−/−</sup></i> MEFs treated overnight with OA and IFNγ. (<b>D</b>) Cells were treated overnight with OA and IFNγ and stained with anti-Irgb10, BODIPY and Hoechst. Representative images are shown. Overlap in fluorescence signals derived from anti-Irgb10 and BODIPY stains is shown for these representative images. Data were analyzed as described in <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003414#s4" target="_blank">Materials and Methods</a> and representative data of three independent experiments are shown. Statistical significance of group values relative to wildtype and between marked groups is shown (***, p<0.005). (<b>E</b>) LDs and total cell lysate were obtained from wildtype, <i>Irgm1/m3<sup>−/−</sup></i> and <i>Atg5</i><sup>−/−</sup> MEFs treated overnight with OA +/− IFNγ and analyzed by immunoblotting.</p
Chlamydia trachomatis is the most commonly reported agent of sexually transmitted bacterial infec... more Chlamydia trachomatis is the most commonly reported agent of sexually transmitted bacterial infections worldwide. This pathogen frequently leads to persistent, long-term, subclinical infections, which in turn may cause severe pathology in susceptible hosts. This is in part due to the strategies that Chlamydia trachomatis uses to survive within epithelial cells and to evade the host immune response, such as subverting intracellular trafficking, interfering signaling pathways and preventing apoptosis. Innate immune receptors such as toll-like receptors expressed on epithelial and immune cells in the genital tract mediate the recognition of chlamydial molecular patterns. After bacterial recognition, a subset of pro-inflammatory cytokines and chemokines are continuously released by epithelial cells. The innate immune response is followed by the initiation of the adaptive response against Chlamydia trachomatis, which in turn may result in T helper 1-mediated protection or in T helper 2-m...
OBJECTIVE Detecting traces of ancient DNA of Vibrio cholerae to provide genetic information assoc... more OBJECTIVE Detecting traces of ancient DNA of Vibrio cholerae to provide genetic information associated with the fifth cholera pandemic. MATERIALS Sediment samples from the sacral foramina of four individuals were analyzed, recovered from a mass grave near an institution dedicated exclusively to the isolation and treatment of citizens infected with cholera in the late 19th century in the city of Cordoba, Argentina. METHODS Paleogenetic techniques (ancient DNA extraction, PCR amplification, and Sanger sequencing) were applied. Specific primers for Vibrio cholerae (VCR, ctxA, ctxB, and tcpA) were designed. RESULTS By amplifying and sequencing the Vibrio cholerae repeats fragment, the infection in at least one individual was confirmed. CONCLUSIONS The synthesis of the paleogenetic results with the archaeological and historical evidence strongly supports that at least one individual from the mass grave in Cordoba, Argentina, was a victim of the fifth cholera pandemic. SIGNIFICANCE Confirming the presence of the disease through multiple lines of evidence, including genetic, archaeological, and historical analyses, strengthens and affirms our understanding of the presence, effects, and potential evolutionary paths of the disease in the past. LIMITATIONS Vibrio cholerae repeats were sequenced in one individual, while the remaining genes could not be amplified, which is likely related to gene copy number. SUGGESTIONS FOR FUTURE RESEARCH Paleogenetic examination of ancient samples from different locations will broaden our understanding of the origin, evolution, and past dissemination of Vibrio cholerae epidemic strains.
Annual Review of Cell and Developmental Biology, Nov 10, 2012
Lipid droplets (LDs) are neutral lipid storage organelles ubiquitous to eukaryotic cells. It is i... more Lipid droplets (LDs) are neutral lipid storage organelles ubiquitous to eukaryotic cells. It is increasingly recognized that LDs interact extensively with other organelles and that they perform functions beyond passive lipid storage and lipid homeostasis. One emerging function for LDs is the coordination of immune responses, as these organelles participate in the generation of prostaglandins and leukotrienes, which are important inflammation mediators. Similarly, LDs are also beginning to be recognized as playing a role in interferon responses and in antigen cross presentation. Not surprisingly, there is emerging evidence that many pathogens, including hepatitis C and Dengue viruses, Chlamydia, and Mycobacterium, target LDs during infection either for nutritional purposes or as part of an anti-immunity strategy. We here review recent findings that link LDs to the regulation and execution of immune responses in the context of host-pathogen interactions.
IntroductionInfection with Human Papillomavirus (HPV) is a recognized risk factor for Chlamydia t... more IntroductionInfection with Human Papillomavirus (HPV) is a recognized risk factor for Chlamydia trachomatis (CT) infection and vice versa. Coinfection of HPV and CT in women is a very common and usually asymptomatic finding that has been linked to increased risk of cervical cancer. It has been demonstrated that CT facilitates the entry of multiple high risk HPV genotypes, leading to damage of the mucosal barrier and interfering with immune responses and viral clearance, which ultimately favours viral persistence and malignant transformation. Although the facilitating effects elicited by CT infection on viral persistence have been reported, little is known about the consequences of HPV infection on CT development.MethodsHerein, we took advantage of a genetically modified human cervical cell line co-expressing HPV-16 major oncogenic proteins E6 and E7, as an experimental model allowing to investigate the possible effects that HPV infection would have on CT development.Results and disc...
Chlamydia trachomatis is an obligate intracellular pathogen and the leading bacterial cause of se... more Chlamydia trachomatis is an obligate intracellular pathogen and the leading bacterial cause of sexually transmitted infections worldwide. Chlamydia trachomatis genovars L1–L3 are responsible for lymphogranuloma venereum (LGV), an invasive sexually transmitted disease endemic in tropical and subtropical regions of Africa, South America, the Caribbean, India and South East Asia. The typical signs and symptoms of C. trachomatis LGV urogenital infections in men include herpetiform ulcers, inguinal buboes, and/or lymphadenopathies. Since 2003, endemic cases of proctitis and proctocolitis caused by C. trachomatis LGV emerged in Europe, mainly in HIV-positive men who have sex with men (MSM). Scarce data have been reported about unusual clinical presentations of C. trachomatis LGV urogenital infections. Herein, we report a case of a 36-year-old heterosexual, HIV-negative male declaring he did not have sex with men or trans women, who presented to the Urology and Andrology outpatient clinic ...
a<p>The predicted stem-loop structures and origin of these small RNAs is depicted in <a ... more a<p>The predicted stem-loop structures and origin of these small RNAs is depicted in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0106434#pone.0106434.s004" target="_blank">Fig. S4</a>.</p><p>Top 10 small RNA reads of <i>M. smegmatis</i>.</p
<p>(<b>A</b>) Wildtype MEFs were treated overnight with OA and IFNγ and immunos... more <p>(<b>A</b>) Wildtype MEFs were treated overnight with OA and IFNγ and immunostained for endogenous Irgm3 and for LDs using BODIPY. (<b>B</b>) Wildtype MEFs were transfected with the three mouse paralogs Irgm1-3 tagged with V5, infected with <i>C. trachomatis</i> and treated with OA and IFNγ at 3 hpi. Cells were fixed at 20 hpi and stained with anti-V5, BODIPY and Hoechst. White arrows point at inclusions. (<b>C</b>) The localization of the GKS proteins Irga6 and Irgb6 were visualized in wildtype and <i>Irgm1/m3<sup>−/−</sup></i> MEFs treated overnight with OA and IFNγ. (<b>D</b>) Cells were treated overnight with OA and IFNγ and stained with anti-Irgb10, BODIPY and Hoechst. Representative images are shown. Overlap in fluorescence signals derived from anti-Irgb10 and BODIPY stains is shown for these representative images. Data were analyzed as described in <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003414#s4" target="_blank">Materials and Methods</a> and representative data of three independent experiments are shown. Statistical significance of group values relative to wildtype and between marked groups is shown (***, p<0.005). (<b>E</b>) LDs and total cell lysate were obtained from wildtype, <i>Irgm1/m3<sup>−/−</sup></i> and <i>Atg5</i><sup>−/−</sup> MEFs treated overnight with OA +/− IFNγ and analyzed by immunoblotting.</p
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