Friday, November 2, 2012

2 On Tick Spit, Immune Evasion, and Round Bodies

There has been much interest in the relationship between tick saliva and the immune response to Borrelia burgdorferi in their host mammals - both animal and human. Recently, the following paper, "Neutrophil Extracellular Traps Entrap and Kill Borrelia burgdorferi Sensu Stricto Spirochetes and Are Not Affected by Ixodes ricinus Tick Saliva", from the Journal of Immunology added to data on how tick saliva affects the immune response at the bite site in a murine model, and may also explain what happens in humans bitten by Ixodes ricinus ticks.

J Immunol. 2012 Oct 29. [Epub ahead of print]

Neutrophil Extracellular Traps Entrap and Kill Borrelia burgdorferi Sensu Stricto Spirochetes and Are Not Affected by Ixodes ricinus Tick Saliva.

Menten-Dedoyart C, Faccinetto C, Golovchenko M, Dupiereux I, Van Lerberghe PB, Dubois S, Desmet C, Elmoualij B, Baron F, Rudenko N, Oury C, Heinen E, Couvreur B.
Laboratory of Human Histology-Centre de Recherche sur les Protéines Prion, University of Liège, B-4000 Liège, Belgium;

Abstract

Lyme disease is caused by spirochetes of the Borrelia burgdorferi sensu lato complex. They are transmitted mainly by Ixodes ricinus ticks. After a few hours of infestation, neutrophils massively infiltrate the bite site. They can kill Borrelia via phagocytosis, oxidative burst, and hydrolytic enzymes. However, factors in tick saliva promote propagation of the bacteria in the host even in the presence of a large number of neutrophils.

The neutrophil extracellular trap (NET) consists of the extrusion of the neutrophil's own DNA, forming traps that can retain and kill bacteria. The production of reactive oxygen species is apparently associated with the onset of NETs (NETosis).

In this article, we:
  • Describe NET formation at the tick bite site in vivo in mice.
  • Show that Borrelia burgdorferi sensu stricto spirochetes become trapped and killed by NETs in humans and that the bacteria do not seem to release significant nucleases to evade this process.
  • Show that saliva from I. ricinus did not affect NET formation by human neutrophils or its stability. However, it greatly decreased neutrophil reactive oxygen species production, suggesting that a strong decrease of hydrogen peroxide does not affect NET formation.
  • Demonstrate that round bodies trapped in NETs were observed, some of them staining as live bacteria.

This observation could help contribute to a better understanding of the early steps of Borrelia invasion and erythema migrans formation after tick bite.

Source: http://www.ncbi.nlm.nih.gov/pubmed/23109724

Comments:

Previous research on Ixodes scapularis and Ixodes ricinus ticks has shown that these ticks' saliva proteins have a negative effect on neutrophils, such as:

Use of CFSE staining of borreliae in studies on the interaction between borreliae and human neutrophils
Inhibition of Neutrophil Function by Two Tick Salivary Proteins
Tick Saliva Reduces Adherence and Area of Human Neutrophils
Horizon Press: Vector-Host Interactions In Disease Transmission

In this new research, there is evidence that even if neutrophils do not kill Borrelia burgdorferi spirochetes from I. ricinus ticks - that NETS stand a chance of killing them instead. And that when neutrophils form NETS, spirochetes found trapped in them often form round bodies which are alive.

What are NETS?

To quote "Neutrophil extracellular traps: Is immunity the second function of chromatin?":

"Neutrophil extracellular traps (NETs) are made of processed chromatin bound to granular and selected cytoplasmic proteins. NETs are released by white blood cells called neutrophils, maybe as a last resort, to control microbial infections. This release of chromatin is the result of a unique form of cell death, dubbed “NETosis.”"

At the above link, readers may watch a video of NETS being formed from neutrophils.

It is not known from this abstract which interactions between spirochetes and human cells took place or if the interaction in humans was extrapolated from a murine model. A reading of the full text is necessary for greater understanding.

More on neutrophil extracellular traps:
http://en.wikipedia.org/wiki/Neutrophil_extracellular_traps
http://jcb.rupress.org/content/198/5/773.full


2 comments:

  1. OC,
    I don't think you are getting any closer to problem solving by delving into such "research".
    It's essential to fight back / get control over those B.b forms which, in the LATE stage of infection, manage to evade both the human immune system and the AB attacks.
    chen-men

    ReplyDelete
  2. Chen-men,

    I'm interested in all stages of Lyme disease because there's a chance that early Lyme disease needs to be better understood - and in understanding it better, one may be able to prevent cases from becoming late stage.

    It is notable that up to 10% of early acute Lyme disease cases result in treatment failures. Why is that? And isn't that important to know, because the longer an infection fails to be treated properly, the more the patient will suffer, and the harder infection will be to beat.

    It is also notable that Dr. Fallon of Columbia University looked at studies in Norway and found a relationship between developing neuroborreliosis and developing chronic Lyme disease. Even if patients were treated, they went on to develop persisting symptoms, many neurological in nature. So treating early neuroborreliosis effectively can prevent chronic problems later.

    In terms of different forms of Borrelia, this is something that needs to be better characterized. What is the composition of different forms of Borrelia, and are those morphological changes really going to deflect antibiotics from doing their job or not?

    I ask that question, because it appears forms of Borrelia really aren't at issue in any of Dr. Stephen Barthold's research. He has found spirochetes in animals after antibiotic treatment, and they are always in the motile form and not a round body or spheroplast form. That they're still present is of interest to many people - but even more so, we have to find out if they are viable. That's the research that he and Dr. Monica Embers and Dr. Kim Lewis are working on now - research on the possibility of Borrelia persister cells after antibiotic use.

    CO

    ReplyDelete

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