Thursday, April 5, 2012

3 Abstract: Population Dynamics Of Borrelia burgdorferi In Lyme Disease.

Credit goes to Joanne, of the Looking at Lyme blog, for mentioning this abstract: It describes a response to Borrelia burgdorferi infection in mice where the first immune response almost clears the infection - but approximately 1 week post infection, the bacterial population recovers and reaches an even larger size before entering the chronic phase.

Front Microbiol. 2012;3:104. Epub 2012 Mar 22.
Population Dynamics of Borrelia burgdorferi in Lyme Disease.
Binder SC, Telschow A, Meyer-Hermann M.

Department of Systems Immunology, Helmholtz Centre for Infection Research Braunschweig, Germany.


Many chronic inflammatory diseases are known to be caused by persistent bacterial or viral infections. A well-studied example is the tick-borne infection by the gram-negative spirochaetes of the genus Borrelia in humans and other mammals, causing severe symptoms of chronic inflammation and subsequent tissue damage (Lyme Disease), particularly in large joints and the central nervous system, but also in the heart and other tissues of untreated patients.

Although killed efficiently by human phagocytic cells in vitro, Borrelia exhibits a remarkably high infectivity in mice and men. In experimentally infected mice, the first immune response almost clears the infection. However, approximately 1 week post infection, the bacterial population recovers and reaches an even larger size before entering the chronic phase.

We developed a mathematical model describing the bacterial growth and the immune response against Borrelia burgdorferi in the C3H mouse strain that has been established as an experimental model for Lyme disease.

The peculiar dynamics of the infection exclude two possible mechanistic explanations for the regrowth of the almost cleared bacteria.

Neither the hypothesis of bacterial dissemination to different tissues nor a limitation of phagocytic capacity were compatible with experiment.

The mathematical model predicts that Borrelia recovers from the strong initial immune response by the regrowth of an immune-resistant sub-population of the bacteria. The chronic phase appears as an equilibration of bacterial growth and adaptive immunity.

This result has major implications for the development of the chronic phase of Borrelia infections as well as on potential protective clinical interventions.

(Special thanks to Frontiers in Microbiology journal for having what appears to be a solid peer review process and Creative Commons license.)


I can't wait to read the full text of this paper. This is an intriguing abstract and it leads to more questions.

How did these researchers come up with their mathematical model? Have other researchers previously observed this second wave of bacteria during infection? What about evidence of peaks in immune response in Borrelia burgdorferi infected animal models which have been documented?

In which way, precisely, is the regrowing immune-resistant sub-population actually immune-resistant? What is happening to B cells and T cells in relationship to this second phase of Borrelia?

From Fig. 3 of Tunev et al., 2011.  Day 8 of infection.  The arrows point to intact extracellular B. burgdorferi in the subcapsular sinus of the lymph node, which was culture positive beginning on day 1 of infection.   Source

Do these phases respond with plasma B cells containing low quality antibodies in germinal centers?

Is there typical somatic hypermutation and antigen affinity or not? What is happening to the T-cell independent response?

And does this model have any implication for antibiotic treatment? As in: Does this second immune-resistant sub-population also have a different response to antibiotics than the initial wave? This model is about infection without treatment, and it is not discussed what the implications could be.

Lots of questions here...

UPDATE: Joanne has informed me the free full text is available online. See:


  1. link to the full paper.
    Comments "Bb efficiently **almost all** killed by phagocytosis", "regrowth of an immune-resistant subpopulation" "The chronic phase appears as an equilibration of bacterial growth and adaptive immunity." Hmm ALMOST not good enough.
    REGROWTH - yes we can vouch for that
    EQUILIBRATION for some of us there is no equilibrium without extensive treatment

  2. Joanne,

    While I did look at Frontiers in Microbiology's web site, I didn't know the full text was available. Thank you.

    I read it, and I'm still absorbing it. The authors' model advises us to consider that Borrelia burgdorferi's survival strategy is not one of dissemination - which there is evidence occurs fairly early on - but more one of affecting the immune system.

    After reading this I have my own hypothesis, and I'm wondering if it can be tested somehow:

    What if there is one population of spirochetes which triggers a strong immune response while a second population operates with more stealth?

    For example, one population spreads through the lymph nodes with some audacity, as Tunev and Barthold have noted - and the other moves through blood and tissue and is less "triggery" to the immune system...

    I am wondering what specifically can lead to an undulatory immune response, too - one in which peaks are observed at 5 weeks and 9 weeks respectively, as mentioned in a recent European study... The authors of this paper only looked at what happened in the mice's immune systems in a matter of days - not weeks. I wish they would have written about the immune response over a longer period of time, and I wish they would also look at non-human primate responses.

    It is all mathematical modeling based on previous studies, though... so someone should be able to come up with a model of their own using different studies and see at which points their own model conforms to other research.

  3. I should be explicit, here, though, and say my hypothesis is based on a chronic infection model and not early infection, which is what the authors of this paper are discussing.


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