scholarly journals Quantification of Brucella abortus population structure in a natural host

2020 ◽  
Author(s):  
Aretha Fiebig ◽  
Catherine E. Vrentas ◽  
Thien Le ◽  
Marianne Huebner ◽  
Paola M. Boggiatto ◽  
...  
Keyword(s):  
Population Structure ◽  
Lymph Node ◽  
Lymph Nodes ◽  
Brucella Abortus ◽  
Microbial Population ◽  
Natural Hosts ◽  
Significant Burden ◽  
Draining Lymph Node ◽  
Microbial Population Dynamics ◽  
Local Lymph Node

AbstractCattle are natural hosts of the intracellular pathogen, Brucella abortus, which inflicts a significant burden on the health and reproduction of these important livestock. The primary routes of infection in field settings have been described, but it is not known how the bovine host shapes the structure of B. abortus populations during infection. We utilized a library of approximately 106 uniquely barcoded B. abortus strains to temporally and spatially quantify population structure at the strain level during colonization of cattle through a natural route of infection. Introducing 108 bacteria from this barcoded library to the conjunctival mucosa resulted in expected levels of local lymph node colonization at a one-week timepoint. We leveraged variance in strain abundance in the library to demonstrate that only 1 in 10,000 brucellae introduced at the site of infection reached the parotid lymph nodes. Thus, cattle restrict the overwhelming majority of B. abortus introduced via the ocular conjunctiva at this dose. Individual strains were spatially restricted within the host tissue, and the total B. abortus census was dominated by a small number of distinct strains in each lymph node. These results define a bottleneck that B. abortus must traverse to colonize local lymph nodes from the conjunctival mucosa. The data further support a model in which a small number of spatially isolated granulomas founded by unique strains are present one-week post infection. These experiments demonstrate the power of barcoded transposon tools to quantify infection bottlenecks and to define pathogen population structure in host tissues.Significance statementUnderstanding microbial population dynamics during infection has important implications for disease management, transmission and pathogen evolution. A quantitative analysis of microbial population structure requires the ability to track individual strains. We used a pool of individually barcoded strains to measure changes in Brucella abortus population structure during infection of bovine hosts via the ocular conjunctiva, a natural route of entry. Cattle exert a severe bottleneck on the bacterial population entering through the conjunctival mucosa such that individual cells have a 0.0001 probability of colonizing a local draining lymph node. The populations in lymph nodes, even on different sides of the same animal, are distinct and dominated by a small number of highly abundant, spatially distinct clones.

scholarly journals Quantification of Brucella abortus population structure in a natural host

2021 ◽  
Vol 118 (11) ◽  
pp. e2023500118
Author(s):  
Aretha Fiebig ◽  
Catherine E. Vrentas ◽  
Thien Le ◽  
Marianne Huebner ◽  
Paola M. Boggiatto ◽  
...  
Keyword(s):  
Population Structure ◽  
Lymph Node ◽  
Brucella Abortus ◽  
Intracellular Pathogen ◽  
Pathogen Population ◽  
Natural Hosts ◽  
Significant Burden ◽  
Local Lymph Node ◽  
Host Tissues ◽  
Time Point

Cattle are natural hosts of the intracellular pathogen Brucella abortus, which inflicts a significant burden on the health and reproduction of these important livestock. The primary routes of infection in field settings have been described, but it is not known how the bovine host shapes the structure of B. abortus populations during infection. We utilized a library of uniquely barcoded B. abortus strains to temporally and spatially quantify population structure during colonization of cattle through a natural route of infection. Introducing 108 bacteria from this barcoded library to the conjunctival mucosa resulted in expected levels of local lymph node colonization at a 1-wk time point. We leveraged variance in strain abundance in the library to demonstrate that only 1 in 10,000 brucellae introduced at the site of infection reached a parotid lymph node. Thus, cattle restrict the overwhelming majority of B. abortus introduced via the ocular conjunctiva at this dose. Individual strains were spatially restricted within the host tissue, and the total B. abortus census was dominated by a small number of distinct strains in each lymph node. These results define a bottleneck that B. abortus must traverse to colonize local lymph nodes from the conjunctival mucosa. The data further support a model in which a small number of spatially isolated granulomas founded by unique strains are present at 1 wk postinfection. These experiments demonstrate the power of barcoded transposon tools to quantify infection bottlenecks and to define pathogen population structure in host tissues.

scholarly journals Microbial population changes during managed aquifer recharge (MAR)

2009 ◽  
Vol 30 (1) ◽  
pp. 33
Author(s):  
Simon Toze ◽  
Deborah Reed
Keyword(s):  
Water Quality ◽  
Population Dynamics ◽  
Population Structure ◽  
Microbial Population ◽  
Managed Aquifer Recharge ◽  
Quality Changes ◽  
Aquifer Recharge ◽  
Population Changes ◽  
Recycled Water ◽  
Microbial Population Dynamics

Managed aquifer recharge (MAR) is a technique that can be used to capture and store water in aquifers under managed conditions for later recovery and use for specific purposes. There is a need to predict water quality changes during MAR, particularly when recycled water is used as the recharged water. An understanding of the interaction between the geochemistry of the aquifer and the microbial population dynamics in the groundwater is important for understanding any water quality changes. A study was undertaken to monitor the changes in the microbial population and link this to changes in the geochemistry. The results obtained showed that the recharge of recycled water to aquifers causes a change in microbial population structure which has direct links to corresponding changes in geochemistry.

scholarly journals Evidence of Long-range nerve pathways connecting and coordinating activity in secondary lymph organs

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Victoria Cotero ◽  
Tzu-Jen Kao ◽  
John Graf ◽  
Jeffrey Ashe ◽  
Christine Morton ◽  
...  
Keyword(s):  
Lymph Node ◽  
Lymph Nodes ◽  
Long Range ◽  
Nerve Stimulation ◽  
Immune Cells ◽  
Immune Cell ◽  
Immune Organs ◽  
Organ Systems ◽  
Local Lymph Node ◽  
Stimulation Of

Abstract Background Peripheral nerve reflexes enable organ systems to maintain long-term physiological homeostasis while responding to rapidly changing environmental conditions. Electrical nerve stimulation is commonly used to activate these reflexes and modulate organ function, giving rise to an emerging class of therapeutics called bioelectronic medicines. Dogma maintains that immune cell migration to and from organs is mediated by inflammatory signals (i.e. cytokines or pathogen associated signaling molecules). However, nerve reflexes that regulate immune function have only recently been elucidated, and stimulation of these reflexes for therapeutic effect has not been fully investigated. Methods We utilized both electrical and ultrasound-based nerve stimulation to activate nerve pathways projecting to specific lymph nodes. Tissue and cell analysis of the stimulated lymph node, distal lymph nodes and immune organs is then utilized to measure the stimulation-induced changes in neurotransmitter/neuropeptide concentrations and immune cellularity in each of these sites. Results and conclusions In this report, we demonstrate that activation of nerves and stimulated release of neurotransmitters within a local lymph node results in transient retention of immune cells (e.g. lymphocytes and neutrophils) at that location. Furthermore, such stimulation results in transient changes in neurotransmitter concentrations at distal organs of the immune system, spleen and liver, and mobilization of immune cells into the circulation. This report will enable future studies in which stimulation of these long-range nerve connections between lymphatic and immune organs can be applied for clinical purpose, including therapeutic modulation of cellularity during vaccination, active allergic response, or active auto-immune disease.

Is local lymph node involvement a prognostic factor in paediatric renal cell carcinoma?

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 20014-20014
Author(s):  
P. Indolfi ◽  
G. Bisogno ◽  
G. Cecchetto ◽  
A. Ferrari ◽  
L. Piva ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Lymph Node ◽  
Lymph Nodes ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Lymph Node Involvement ◽  
Number Of Patients ◽  
Node Involvement ◽  
Local Lymph Node

20014 Background: RCC in childhood is rare. Children with RCC tend to have a similar overall prognosis when compared with adults, where prognosis worsens with increasing stage, although direct comparisons of adult and paediatric data isn’t easy. The aim of our study is to identify the prognostic significance of local lymph node involvement in children with Renal Cell Carcinoma (RCC). Methods: On the basis of a retrospective study, the recently founded Italian Association for Paediatric Hematology and Oncology-Rare Tumors Paediatric Age (AIEOP-TREP) identified 16 patients (9 females) with RCC and local lymph node involvement at 10 of these centers. The cases were observed among 59 paediatric RCC, corresponding to 27.1% of RCC presenting in Italy from January 1973 to May 2006. Results: Overall, 9 patients were alive and disease free at last follow-up: eight patients had regional lymph node dissection (RLND) from the diaphragm at the aortic bifurcation, and one had the para-aortic lymph nodes removal. Six patients died: one had RLND (died from progression of disease), three had the renal hilum lymph nodes removal, and two the para-aortic lymph nodes dissection. One patient was lost to follow-up after relapse: this patient had para-aortic lymph node removal at diagnosis. Estimated 25-year DFS and OS rates for all patients were 64.2% and 50.5%, respectively. Given the small number of patients, little can be said about the value, if any, of adjuvant immunotherapy in this group of RCC. Conclusions: Children with lymph node positive RCC had a relatively unfavourable long- term prognosis. In our experience the RLND improves the prognosis. Further investigation of the biologic differences is warranted. Because of the very low incidence of paediatric RCC, an international clinical trial will be required to establish optimal therapy for children with RCC. No significant financial relationships to disclose.

scholarly journals Treatment by limited surgery and specific immunization of guinea pigs with stage II experimental cancer.

1981 ◽  
Vol 154 (2) ◽  
pp. 253-261 ◽  
Author(s):  
J T Hunter ◽  
M P Ashley ◽  
S Sukumar ◽  
T Sugimoto ◽  
B Zbar ◽  
...  
Keyword(s):  
Lymph Node ◽  
Lymph Nodes ◽  
Tumor Cells ◽  
Guinea Pigs ◽  
Lung Metastases ◽  
Stage Ii ◽  
Water Emulsion ◽  
Experimental Cancer ◽  
Limited Surgery ◽  
Draining Lymph Node

The malignant disease produced in guinea pigs by intradermal inoculation of line-10 was allowed to progress to stage II, at which time the dermal tumor and the first draining lymph node were grossly evident. At that stage, the external appearance of the next draining lymph node was normal, but it contained tumor cells. Limited surgery consisting of excision of the dermal tumor and first draining lymph node was not curative; palpable metastases developed in the second and other draining lymph nodes, and at autopsy, some animals were found to have gross, visible lung metastases. Immunization of guinea pigs with a mixture of irradiated syngeneic tumor cells plus mycobacterial cell walls in an oil-in-water emulsion eradicated tumor cells remaining in lymph nodes after limited surgery for stage II experimental cancer and prevented progression of the disease to stage III. Tumor intravenously implanted in the lungs of animals after limited surgery for stage II disease was also eliminated by immunization.

Fate of attenuated schistosomula administered to mice by different routes, relative to the immunity induced againstSchistosoma mansoni

Parasitology ◽  
1989 ◽  
Vol 99 (1) ◽  
pp. 39-45 ◽  
Author(s):  
Patricia S. Coulson ◽  
A. P. Mountford
Keyword(s):  
Lymph Node ◽  
Lymph Nodes ◽  
Injection Site ◽  
The Other ◽  
Intradermal Vaccination ◽  
Vaccination Site ◽  
Onward Migration ◽  
Adequate Stimulus ◽  
Draining Lymph Node ◽  
Newly Transformed Schistosomula

SUMMARYNewly transformed schistosomula and day 8 lung parasites, derived from optimally irradiated cercariae, were used to immunize groups of C57B1/6 mice via 4 different injection routes. Schistosomula administered intradermally induced high levels of protection, comparable with that achieved by percutaneous vaccination. Intermediate levels were elicited by delivery of parasites via intraperitoneal or intratracheal routes. In contrast, intravenous injection of schistosomula to the lungs resulted in little or no resistance. Attenuated day 8 schistosomula administered intradermally were at least as immunogenic as irradiated cercariae. The fate of radio-isotope labelled attenuated lung schistosomula, injected via the various routes, was examined by compressed organ autoradiography. After intradermal vaccination, a proportion of parasites migrated from the site of injection to the draining lymph node and lungs. Conversely, schistosomula administered via the other 3 routes persisted to varying degrees at the injection site, but little onward migration was observed. We suggest that successful vaccination requires that some attenuated parasites migrate to, and sequester in, lymph nodes draining the vaccination site; persistence at the site of administration alone is not an adequate stimulus.

scholarly journals Lymph Node Morphology in Stage II Colorectal Cancer

2020 ◽  
Author(s):  
Annabelle Greenwood ◽  
John Keating ◽  
Diane Kenwright ◽  
Ali Shekouh ◽  
Alex Dalzell ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Risk Factors ◽  
Lymph Node ◽  
Lymph Nodes ◽  
B Cell ◽  
Stage Ii ◽  
Cell Compartments ◽  
Stage Ii Colorectal Cancer ◽  
Draining Lymph Node ◽  
Draining Lymph Nodes

ABSTRACTBackgroundColorectal cancer is one of the leading causes of cancer-associated morbidity and mortality worldwide. The local anti-tumour immune response is particularly important for patients with stage II where the tumour-draining lymph nodes have not yet succumbed to tumour spread. The lymph nodes allow for the expansion and release of B cell compartments such as primary follicles and germinal centres. A variation in this anti-tumour immune response may influence the observed clinical heterogeneity in stage II patients.AimThe aim of this study was to explore tumour-draining lymph node histomorphological changes and tumour pathological risk factors including the immunomodulatory microRNA-21 (miR-21) in a small cohort of stage II CRC.MethodsA total of 23 stage II colorectal cancer patients were included. Tumour and normal mucosa samples were analysed for miR-21 expression levels and B-cell compartments were quantified from Haematoxylin and Eosin slides of lymph nodes. These measures were compared to clinicopathological risk factors such as perforation, bowel obstruction, T4 stage and high-grade.ResultsWe observed greater follicle density in patients with a lower tumour T stage and higher germinal centre density in patients with higher pre-operative carcinoembryonic antigen levels. Trends were also detected between tumours with deficiency in mismatch repair proteins, lymphatic invasion and both the density and size of B-cell compartments. Lastly, elevated tumour miR-21 was associated with decreased follicle and germinal centre size.ConclusionVariation in B-cell compartments of tumour-draining lymph nodes is associated with clinicopathological risk factors in stage II CRC patients.What does this paper add to the literature?This study demonstrates the variability of tumour draining lymph node morphological features in stage II CRC patients. This provides new scope for biomarker discovery in stage II CRC patients which is a research priority for this patient group.

scholarly journals Coformulation with tattoo ink for immunological assessment of vaccine immunogenicity in the draining lymph node

2020 ◽  
Author(s):  
Isaac M Barber-Axthelm ◽  
Hannah G Kelly ◽  
Robyn Esterbauer ◽  
Kathleen Wragg ◽  
Anne Gibbon ◽  
...  
Keyword(s):  
Lymph Node ◽  
T Cell ◽  
Lymph Nodes ◽  
Vaccine Development ◽  
T Cell Responses ◽  
Vaccine Antigen ◽  
Cell Responses ◽  
Visual Identification ◽  
Draining Lymph Node ◽  
Vaccine Immunogenicity

AbstractCharacterisation of germinal centre B and T cell responses yields critical insights into vaccine immunogenicity. Non-human primates are a key pre-clinical animal model for human vaccine development, allowing both lymph node and circulating immune responses to be longitudinally sampled for correlates of vaccine efficacy. However, patterns of vaccine antigen drainage via the lymphatics after intramuscular immunisation can be stochastic, driving uneven deposition between lymphoid sites, and between individual lymph nodes within larger clusters. In order to improve the accurate isolation of antigen-exposed lymph nodes during biopsies and necropsies, we developed and validated a method for co-formulating candidate vaccines with tattoo ink, which allows for direct visual identification of vaccine-draining lymph nodes and evaluation of relevant antigen-specific B and T cell responses by flow cytometry. This approach improves the assessment of vaccine-induced immunity in highly relevant non-human primate models.

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