Diagnosis of Mediterranean spotted fever by cultivation of Rickettsia conorii from blood and skin samples using the centrifugation-shell vial technique and by detection of R. conorii in circulating endothelial cells: a 6-year follow-up.

1996 ◽  
Vol 34 (11) ◽  
pp. 2722-2727 ◽  
Author(s):  
B La Scola ◽  
D Raoult
Keyword(s):  
Endothelial Cells ◽  
Spotted Fever ◽  
Circulating Endothelial Cells ◽  
Rickettsia Conorii ◽  
Mediterranean Spotted Fever ◽  
Shell Vial ◽  
Skin Samples

scholarly journals Beta Interferon-Mediated Activation of Signal Transducer and Activator of Transcription Protein 1 Interferes with Rickettsia conorii Replication in Human Endothelial Cells

2011 ◽  
Vol 79 (9) ◽  
pp. 3733-3743 ◽  
Author(s):  
Punsiri M. Colonne ◽  
Marina E. Eremeeva ◽  
Sanjeev K. Sahni
Keyword(s):  
Endothelial Cells ◽  
Neutralizing Antibodies ◽  
Spotted Fever ◽  
Janus Kinase ◽  
Rickettsia Conorii ◽  
Mediterranean Spotted Fever ◽  
Signal Transducer ◽  
Microvascular Endothelium ◽  
Content Type ◽  
Beta Interferon

ABSTRACTInfection of the endothelial cell lining of blood vessels withRickettsia conorii, the causative agent of Mediterranean spotted fever, results in endothelial activation. We investigated the effects ofR. conoriiinfection on the status of the Janus kinase (JAK)-signal transducer and activator of transcription protein (STAT) signaling pathway in human microvascular endothelial cells (HMECs), the most relevant host cell type, in light of rickettsial tropism for microvascular endotheliumin vivo.R. conoriiinfection induced phosphorylation of STAT1 on tyrosine 701 and serine 727 at 24, 48, and 72 h postinfection in HMECs. Employing transcription profile analysis and neutralizing antibodies, we further determined that beta interferon (IFN-β) production and secretion are critical for STAT1 activation. Secreted IFN-β further amplified its own expression via a positive-feedback mechanism, while expression of transcription factors interferon regulatory factor 7 (IRF7) and IRF9, implicated in the IFN-β–STAT1 feedback loop, was also induced. Metabolic activity of rickettsiae was essential for the IFN-β-mediated response(s) because tetracycline treatment inhibitedR. conoriireplication, IFN-β expression, and STAT1 phosphorylation. Inclusion of IFN-β-neutralizing antibody during infection resulted in significantly enhancedR. conoriireplication, whereas addition of exogenous IFN-β had the opposite inhibitory effect. Finally, small interfering RNA-mediated knockdown further confirmed a protective role for STAT1 against intracellularR. conoriireplication. In concert, these findings implicate an important role for IFN-β-mediated STAT1 activation in innate immune responses of vascular endothelium toR. conoriiinfection.

scholarly journals Significant Growth by Rickettsia Species within Human Macrophage-Like Cells Is a Phenotype Correlated with the Ability to Cause Disease in Mammals

Pathogens ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 228
Author(s):  
M. Nathan Kristof ◽  
Paige E. Allen ◽  
Lane D. Yutzy ◽  
Brandon Thibodaux ◽  
Christopher D. Paddock ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Spotted Fever ◽  
Growth Characteristic ◽  
Human Macrophage ◽  
Rickettsia Conorii ◽  
Spotted Fever Group ◽  
Rocky Mountain Spotted Fever ◽  
Phagocytic Cells ◽  
Pathogenic Potential ◽  
Rickettsia Species

Rickettsia are significant sources of tick-borne diseases in humans worldwide. In North America, two species in the spotted fever group of Rickettsia have been conclusively associated with disease of humans: Rickettsia rickettsii, the causative agent of Rocky Mountain spotted fever, and Rickettsia parkeri, the cause of R. parkeri rickettsiosis. Previous work in our lab demonstrated non-endothelial parasitism by another pathogenic SFG Rickettsia species, Rickettsia conorii, within THP-1-derived macrophages, and we have hypothesized that this growth characteristic may be an underappreciated aspect of rickettsial pathogenesis in mammalian hosts. In this work, we demonstrated that multiple other recognized human pathogenic species of Rickettsia, including R. rickettsii, R. parkeri, Rickettsia africae, and Rickettsiaakari can grow within target endothelial cells as well as within PMA-differentiated THP-1 cells. In contrast, Rickettsia bellii, a Rickettsia species not associated with disease of humans, and R. rickettsii strain Iowa, an avirulent derivative of pathogenic R. rickettsii, could invade both cell types but proliferate only within endothelial cells. Further analysis revealed that similar to previous studies on R. conorii, other recognized pathogenic Rickettsia species could grow within the cytosol of THP-1-derived macrophages and avoided localization with two different markers of lysosomal compartments; LAMP-2 and cathepsin D. R. bellii, on the other hand, demonstrated significant co-localization with lysosomal compartments. Collectively, these findings suggest that the ability of pathogenic rickettsial species to establish a niche within macrophage-like cells could be an important factor in their ability to cause disease in mammals. These findings also suggest that analysis of growth within mammalian phagocytic cells may be useful to predict the pathogenic potential of newly isolated and identified Rickettsia species.

scholarly journals Assessment of the Percentages of T-lymphocyte Subsets in the Peripheral Blood of Mediterranean Spotted Fever Patients

2020 ◽  
Vol 18 (2) ◽  
pp. 111-119
Author(s):  
Iv. Baltadzhiev ◽  
P. Pavlov
Keyword(s):  
T Cells ◽  
Disease Severity ◽  
T Lymphocyte ◽  
Lymphocyte Subsets ◽  
Spotted Fever ◽  
Healing Process ◽  
Cell Subset ◽  
Rickettsia Conorii ◽  
Mediterranean Spotted Fever ◽  
T Lymphocyte Subsets

Purpose: Mediterranean spotted fever (MSF) is a rickettsial disease. The aim was to evaluate the host immunе response to Rickettsia conorii. Material and methods: 62 patients were assigned into three groups: with mild, moderate or severe clinical forms of MSF. Controls were 32 healthy individuals. The diagnosis of MSF was confirmed by the indirect immunofluorescence assay. Immunophenotyping was performed using Epics XL-MCL Coulter. Results: The percentage of immune competent (CD3+) cells decreased, whereas that of helper/inducer (CD3+CD4+) and suppressor/cytotoxic (CD3+CD8+) did not change compared to controls. All three T-cell subset percentages did not parallel the disease severity. Naïve T-cells (CD4+CD45RA+) showed reduced levels, whereas activated memory (CD4+CD45RO+) T-cells did not change significantly. The percentage of activated (CD3+HLA-DR+) T-cells increased regardless of the disease severity, till the rise of stimulatory molecules (CD38+total) matched the disease severity forms. The percentage of costimulatory CD28-molecules corresponded to the disease severity as their levels increased significantly in mild forms and showed an evident downward trend towards the severe ones. Conclusion: Reduced T-lymphocyte subsets are likely related to trans-migration into perivascular inflammatory foci. The increased percentage of T-lymphocytes armed with stimulatory molecules probably reflects the mobilization of cell-mediated immune response in the healing process.

scholarly journals Nonselective Persistence of a Rickettsia conorii Extrachromosomal Plasmid during Mammalian Infection

2016 ◽  
Vol 84 (3) ◽  
pp. 790-797 ◽  
Author(s):  
Sean P. Riley ◽  
Abigail I. Fish ◽  
Daniel A. Garza ◽  
Kaikhushroo H. Banajee ◽  
Emma K. Harris ◽  
...  
Keyword(s):  
Pathogenic Bacteria ◽  
Genetic Manipulation ◽  
Fluorescent Proteins ◽  
Spotted Fever ◽  
Rickettsia Conorii ◽  
Mediterranean Spotted Fever ◽  
Extrachromosomal Dna ◽  
Content Type

Scientific analysis of the genusRickettsiais undergoing a rapid period of change with the emergence of viable genetic tools. The development of these tools for the mutagenesis of pathogenic bacteria will permit forward genetic analysis ofRickettsiapathogenesis. Despite these advances, uncertainty still remains regarding the use of plasmids to study these bacteria inin vivomammalian models of infection, namely, the potential for virulence changes associated with the presence of extrachromosomal DNA and nonselective persistence of plasmids in mammalian models of infection. Here, we describe the transformation ofRickettsia conoriiMalish 7 with the plasmid pRam18dRGA[AmTrCh]. TransformedR. conoriistably maintains this plasmid in infected cell cultures, expresses the encoded fluorescent proteins, and exhibits growth kinetics in cell culture similar to those of nontransformedR. conorii. Using a well-established murine model of fatal Mediterranean spotted fever, we demonstrate thatR. conorii(pRam18dRGA[AmTrCh]) elicits the same fatal outcomes in animals as its untransformed counterpart and, importantly, maintains the plasmid throughout infection in the absence of selective antibiotic pressure. Interestingly, plasmid-transformedR. conoriiwas readily observed both in endothelial cells and within circulating leukocytes. Together, our data demonstrate that the presence of an extrachromosomal DNA element in a pathogenic rickettsial species does not affect eitherin vitroproliferation orin vivoinfectivity in models of disease and that plasmids such as pRam18dRGA[AmTrCh] are valuable tools for the further genetic manipulation of pathogenic rickettsiae.

Level of activated circulating endothelial cells to predict progression-free survival of Anlotinib treatment in patients with NSCLC: Analysis on ALTER-0303 study.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e20530-e20530 ◽  
Author(s):  
Kai LI ◽  
Jing Wang ◽  
Xinyue Wang ◽  
Zhujun Liu ◽  
Cuigui Zhang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Initial Period ◽  
Progression Free Survival ◽  
Circulating Endothelial Cells ◽  
Free Survival ◽  
Time Points ◽  
Potential Biomarker ◽  
Nsclc Patients ◽  
Clinical Trial Information

e20530 Background: Activated circulating endothelial cells (aCECs) have been indicated as a potential biomarker of angiogenesis in a variety of cancers. Several studies have revealed that aCECs may reflect the extent of tumor angiogenesis, and the level of aCECs counts may has correlation with progression-free survival (PFS) in anti-angiogenesis therapy on NSCLC patients. Therefore, we investigated the association between aCECs and PFS of Anlotinib treatment in ALTER-0303 study. Methods: NSCLC patients with aCECs counts in ALTER-0303 study were observed. Samples were prospectively collected at six time points: before treatment (baseline), on the 7th, 15th, 21th, 42th, 63thday of Anlotinib treatment. aCECs was identified by Flow cytometry (FCM). The prognostic value of aCECs counts was analyzed and, the patients were stratified according to their ratio of the minimum aCECs counts in all time points and counts on baseline (aCECs min/baseline) as <1 and ≥1. Results: Forty-nine patients were included of which 35 and 14 had an aCECs min/baseline<1 and ≥1, respectively in Anlotinib arm. Median follow-up was 8.6 months. In univariate survival analysis, patients with min/baseline<1 had longer PFS [HR=0.439, 95% CI (0.211-0.912), P = 0.023], the median PFS for the patients with aCECs min/baseline <1 and ≥1 were 193 days and 124 days, respectively (shown in Table). However, there were no significant relation between PFS and such aCECs min/baseline ratio found in control arm of ALTER-0303 study. Conclusions: A decrease of aCECs counts from baseline during an initial period of Anlotinib therapy may predict longer PFS and good response in NSCLC patients. Information: NCT02029209, NCT02388919 Clinical trial information: NCT02029209. [Table: see text]

Circulating Endothelial Cells as a Biomarker in Non-Small Cell Lung Cancer Patients: Correlation with Clinical Outcome

2014 ◽  
Vol 29 (4) ◽  
pp. 337-344 ◽  
Author(s):  
Fadi Najjar ◽  
Moosheer Alammar ◽  
Marroan Bachour ◽  
Ghassan Al-Massarani
Keyword(s):  
Lung Cancer ◽  
Endothelial Cells ◽  
Small Cell Lung Cancer ◽  
Healthy Volunteers ◽  
Small Cell ◽  
Circulating Endothelial Cells ◽  
Newly Diagnosed ◽  
Small Cell Lung ◽  
Nsclc Patients

Background Circulating endothelial cells (CECs) have been proposed as a biomarker for the assessment of patients with solid tumors. However, few data are available in non-small cell lung cancer (NSCLC). We therefore analyzed the clinical significance of CECs in newly diagnosed NSCLC patients. In addition, we tried to determine the prognostic value of CECs in NSCLC. Methods In this prospective study, 151 newly diagnosed NSCLC patients and 25 healthy volunteers were included. Furthermore, 25 patients with a partial response (n=15) or stable disease (n=10) after treatment were evaluated at recurrence with a mean follow-up of 117 days (range: 47-364 days). CECs were counted using magnetic beads coupled to a specific antibody against CD146. Results The pre-treatment CEC count was significantly higher in patients with all histological subtypes of NSCLC than in healthy volunteers (p<0.0001). High baseline CEC counts were significantly correlated with advanced clinical stages (p=0.026), weight loss (p=0.03), and poorly differentiated NSCLC (p=0.02). The amount of CECs increased significantly at recurrence compared with their amount after treatment in 20/21 assessable patients (p=0.0001). Nevertheless, there was no significant correlation between baseline CEC count and median duration of progression-free survival (p=0.402). Conclusions Increased CEC counts were present in patients with newly diagnosed NSCLC compared with healthy subjects. Elevated levels of baseline CECs correlated with high-risk factors in NSCLC. In addition, increased CEC count during follow-up seems to be correlated with recurrence in NSCLC patients.

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