"Cell death due to Borrelia infection" (Schwartz2)


Main funder


Funds granted by main funder (€)

84 093,54


Funding program

Others (Funding programs)


Project timetable

Project start date: 01/01/2018

Project end date: 31/12/2018


Summary

The causative agent for Lyme Borreliosis (LB) Borrelia burgdorferi sensu lato, found in Ixodes ticks [3,23], is a pleomorphic bacteria that can alter its form into round bodies (RBs) or biofilm-like formations (BFLs) under unfavorable conditions. For instance, nutritional depletion, changes in pH, even antibiotics can cause these morphological alterations [1,11,12,25]. Furthermore, if the optimal conditions are returned the cells can revert back to the parental spirochetal form [11].

Borrelia species can be found globally. It is thought that the main pathogen in the USA is Borrelia burgdorferi sensu stricto (henceforth referred to as B. burgdorferi), whilst in Europe B. garinii and B. afzelii, in addition to B. burgdorferi, are believed to be the leading causes for human diseases [17,22]. These pathogens can cause a variety of signs and symptoms ranging from erythema migrans and arthritis to neurological or cardiac impairments [27]. LB is currently treated with antibiotics only [27]. Yet, there are patients that suffer from what is usually called post-treatment Lyme disease syndrome (PTLDS) [22]. The pleomorphic forms of the bacteria are thought play a major role in the persistence of this disease [2,21,25]. Furthermore, antibiotics have been demonstrated to have a lessened effect on these pleomorphic forms [4,9,19,21]. Hence, LB is becoming major global health threat. In the USA alone the number of LB cases every year is over 300 000 [5]. According to a WHO report, in Europe the number of reported LB cases has increased 10-fold from 1990's to 2010 [8]. Therefore, including the persistent forms of the three species of Borrelia into a pathogenic investigation is imperative.

Apoptosis or programmed cell death is a constant, naturally occurring phenomenon in cells. However, infections can have a proapoptotic effect on cells [10]. Borrelia has been found to cause apoptosis in a variety of cells including neuronal and glial cells from the dorsal root ganglia of rhesus monkeys [14], normal human dermal fibroblasts [16], peripheral T lymphocytes [18] and monocytes [7] among others. As both cardiac and synovial impairments are known consequence of a Borrelia infection, examining the possible pathogenic effects of Borrelia induced cell death on these cells is essential.

In autoimmune diseases the immune cells attack the host's own cells. Currently, over 80 autoimmune diseases affecting approximately 3-5 % of the population worldwide have been identified [13,26]. Moreover, 5-10 % of the western world is suffering from autoimmune diseases [13,20]. Autoimmune-related T helper 17 cells and auto-reactive antigens have been found in LB patients [6,24]. Furthermore, an animal model of Lyme arthritis and Lyme carditis indicate at an autoimmune developmental pathway via molecular mimicry [15]. Because of the autoimmune or autoimmune-like disorder of some LB patients (arthritis, carditis) a question arises of how exactly does the bacteria trigger these diseases? In order to answer this question, we hypothesize that the apoptotic bodies with local chronic inflammation in tissues induced by Borrelia leads to autoimmune or autoimmune-like diseases.


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Last updated on 2020-26-06 at 15:08