24 May 2012
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"Bacterial/Viral Coinfections";
TLR2 (fungi)Signaling Depletes IRAK1 and Inhibits Induction of Type 1 by TLR7/9 (viruses)-- -CV Harding, 2012 (More in the chart at the bottom of this homepage)
"Multiple Mechanisms of Immune Suppression by B Lymphocytes" (New and Trashes Yale and IDSA)
NIH's Treatment Recommendations for Chronic Active Epstein-Borreliosis, the chronic illness also induced by OspA vaccination or exposure to molds.
ELISA = arbitrary cutoff.
Disclaimer
1998, CIA Oilmen & Israelis plan to overthrow Saddam for the oil.
Bush/Gore Oil/War-(Oct,2000)
Bush's own explainer (Oct
2000) re:
Iraq Oil
"This finding indicates that constitutive lymphotropism, as assessed in vitro, is not required for successful colonization of mice. These results also suggest that direct interaction between spirochetes and lymphocytes during mammalian infection is not an artifact of in vitro phenotypic segregation but may be an integral step in the infectious process."
Dave's Home: http://www.niaid.nih.gov/dir/labs/rmlmb.htm
http://iai.asm.org/cgi/content/full/69/3/1428?view=full&pmid=11179308
Shortly after Borrelia burgdorferi was identified as the infectious agent of Lyme disease (3), lymphocytic involvement in both the responses to and pathological effects of this spirochetosis was recognized in patients and experimental animals (1, 4-7, 12-21, 23-25, 28-30, 32, 36). Immune responses have been well studied in Lyme disease (5, 28). In contrast, although numerous studies have reported pathological findings involving lymphocytes, comparatively little is known about the nature of the relationship between the spirochetes and mammalian lymphocytes that lead to manifestations such as lymphopenia (28), inflammatory lymphocytic infiltrations and aggregates (6, 7, 12-17, 19, 23, 25, 29), lymphocytoma (7, 24), pseudo-lymphoma (20), and malignant lymphoma (1, 4, 18, 21, 30). Previous work has shown that B. burgdorferi cells and components, including major surface lipoproteins and extracellular membrane vesicles or blebs, are potent lymphocytic mitogens, inducing polyclonal B-cell proliferation and immunoglobulin M secretion (22, 26, 31, 33-36). More recently, direct adherence, invasion, and killing of both primary and cultured human B and T cells by B. burgdorferi were demonstrated in vitro (10). In that study, spirochetes preferentially targeted human B and T cells in primary mixed mononuclear cell preparations. Both the avidity of spirochetes for lymphocytes and the susceptibility of B and T cells to invasion and killing by the spirochetes were phenotypically selectable. However, significant lymphocytic killing was observed only in coincubation mixtures containing more than one spirochete per lymphocyte, a ratio far exceeding that believed to occur in natural infections (10).
DNA in blebs
| Scanning Microsc Suppl 1989;3:109-15 | Related Articles, Links |
Structural features of Borrelia burgdorferi--the Lyme disease spirochete: silver staining for nucleic acids.
Garon CF, Dorward DW, Corwin MD.
Department of Health and Human Services, National Institutes of Health, National Institute of Allergy and Infectious Diseases, Hamilton, Montana.
Borrelia burgdorferi--the Lyme disease spirochete--was grown in modified Kelly medium and characterized by transmission and by scanning electron microscopy. Using silver staining procedures which preferentially bind to nuclear components of eukaryotic cells, signal could be detected by backscattered electron imaging throughout the length of the prokaryotic spirochete. Interestingly, however, the highest levels of backscattered signal were observed in naturally elaborated membrane blebs that were visible attached to cell surfaces and free in the medium. These membrane vesicles could be enriched by filtration through nitrocellulose or Anopore membranes and by differential centrifugation. The possibility of contaminating cellular DNA coating the membrane vesicles was ruled out by exhaustive digestion with pancreatic DNAse I. Intact DNA was demonstrated both by lysing blebs directly on the surface of microscope grids and by extracting molecules from purified bleb preparation with detergents and solvents. Both linear and circular DNA molecules could be identified in purified membrane blebs. A simple, one-step, alternative silver staining procedure is described which appears to effectively label the protein-nucleic acid complexes contained in the membrane vesicles of the human pathogen B. burgdorferi, and may provide an important method to track and to define the biological function of these structures. PMID: 2482525
Borrelia specifically attacking lymphocytes:
| Clin Infect Dis 1997 Jul;25 Suppl 1:S2-8 | Related Articles, Links |
Invasion and cytopathic killing of human lymphocytes by spirochetes causing Lyme disease.
Dorward DW, Fischer ER, Brooks DM.
National Institute of Allergy and Infectious Diseases, Rocky Mountain Laboratories, Hamilton, Montana 59840, USA.
Lyme disease is a persistent low-density spirochetosis caused by Borrelia burgdorferi sensu lato. Although spirochetes causing Lyme disease are highly immunogenic in experimental models, the onset of specific antibody responses to infection is often delayed or undetectable in some patients. The properties and mechanisms mediating such immune avoidance remain obscure. To examine the nature and consequences of interactions between Lyme disease spirochetes and immune effector cells, we coincubated B. burgdorferi with primary and cultured human leukocytes. We found that B. burgdorferi actively attaches to, invades, and kills human B and T lymphocytes. Significant killing began within 1 hour of mixing. Cytopathic effects varied with respect to host cell lineage and the species, viability, and degree of attenuation of the spirochetes. Both spirochetal virulence and lymphocytic susceptibility could be phenotypically selected, thus indicating that both bacterial and host cell factors contribute to such interactions. These results suggest that invasion and lysis of lymphocytes may constitute previously unrecognized factors in Lyme disease and bacterial pathogenesis.
When spirochetes get the munchies:
http://iai.asm.org/cgi/content/full/69/3/1428?view=full&pmid=11179308
Infection and Immunity, March 2001, p.
1428-1432, Vol. 69, No. 3
0019-9567/01/$04.00+0 DOI: 10.1128/IAI.69.3.1428-1432.2001
Murine Model for Lymphocytic Tropism by Borrelia burgdorferi
Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, Hamilton, Montana 59840
Received 19 October 2000/Returned for modification 30 November 2000/Accepted 7 December 2000
In vitro studies have demonstrated direct interactions between Borrelia burgdorferi and human B and T cells. However, largely because disseminated infections typically occur at very low density, little is known about associations between spirochetes and mammalian host cells in vivo. To assess whether spirochetes interact directly with lymphocytes in mammals, we developed a mouse model for lymphotropism. By repeatedly coincubating spirochetes with primary mouse lymphocytes that were immobilized by adherence to immunomagnetic beads, we were able to preferentially enrich cultures for or against bacteria with constitutive affinity for murine B and T cells. Populations of lymphotropically enriched, stock infectious, and lymphotropically depleted spirochetes were injected intradermally into mice. Lymphocytes were then purified from the blood and spleens of challenged mice and placed into spirochetal culture medium. Cultures of B. burgdorferi were obtained from primary lymphocyte preparations from mice challenged with each of the three populations of spirochetes. Recovery of lymphocyte-associated bacteria occurred within 1 h of challenge with enriched bacteria. Lymphocyte preparations from mice challenged with stock infectious and lymphotropically depleted bacteria produced cultures after 1 day postchallenge. All lymphocyte preparations were culture negative after 1 week. These results demonstrate that lymphotropic B. burgdorferi is infectious in mice and suggest that associations between spirochetes and lymphocytes occur in vivo. The results also suggest that factors involved in lymphocytic binding may be inducible in vivo. Thus, this system provides a model for studying the role of such interactions in mammalian infections.