Chris Kresser article about chronic Lyme Disease being REAL

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TheBrain
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Chris Kresser article about chronic Lyme Disease being REAL

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I received this email this morning from Kresser. The email is available on his web site at https://email.chriskresser.com/chronic- ... clueless-a. (Internal links aren’t below, but they are on the web site.)
I saw an article in New Scientist a few weeks ago called “Chronic Lyme disease may be a misdiagnosis of chronic fatigue syndrome.”

Here are the first two paragraphs:

“Most people who think they have a long-lasting form of Lyme disease, triggered by a tick bite, may really have chronic fatigue syndrome, a panel of UK infectious disease experts said today.

Some people who mistakenly believe they have Lyme disease are endangering their health by taking long courses of antibiotics, leading to other infections such as sepsis, the doctors warned.”

The timing is ironic, given that just two days later, a study was published in the journal Antibiotics called “The Long-Term Persistence of Borrelia burgdorferi Antigens and DNA in the Tissues of a Patient with Lyme Disease.”

Researchers performed an autopsy on a 53-year-old woman from New York who had suffered from Lyme disease for 16 years and had taken multiple courses of antibiotics during that period.

They examined tissues in her brain, heart, kidney, and liver, and found Borrelia burgdorferi—the organism that causes Lyme disease—in all of these organs.

They also found clear evidence of Borrelia biofilms, which is significant because biofilms are known to be antibiotic-resistant. And they detected significant numbers of infiltrating lymphocytes present next to the biofilms, which indicates that Borrelia was causing chronic inflammation.
ApoE 4/4 - When I was in 7th grade, my fellow students in history class called me "The Brain" because I had such a memory for detail. I excelled at memorization and aced tests. This childhood memory helps me cope!
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Re: Chris Kresser article about chronic Lyme Disease being REAL

Post by circular »

TheBrain wrote:I received this email this morning from Kresser. The email is available on his web site at https://email.chriskresser.com/chronic- ... clueless-a. (Internal links aren’t below, but they are on the web site.)
Wow.
ApoE 3/4 > Thanks in advance for any responses made to my posts.
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Re: Chris Kresser article about chronic Lyme Disease being REAL

Post by zc_hl »

The innate immune system is normally able to produce a substance, LL-37, which disrupts biofilms: Human Host Defense Peptide LL-37 Prevents Bacterial Biofilm Formation (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2519444/).

But I guess that it is if your immune system is efficient. The secretion of this peptide is normally regulated by vitamin D but apparently, the vitamin D receptor can be blocked by bacterial byproducts.

"Some intracellular pathogens (e.g. M. tuberculosis and EBV) survive by dysregulating gene expression by the vitamin D nuclear receptor (VDR). Just a decade ago, the VDR was studied almost solely in the context of calcium metabolism. Today, however, this receptor has been shown to express at least 1000 genes, with many more putative gene candidates in the pipeline. VDR promoters are ubiquitous throughout the human genome, and genes already associated with VDR regulation are directly connected to autoimmune and inflammatory processes.
In addition to its key role in transcription regulation, the VDR also lies at the heart of the human innate immune response. It expresses TLR2, which allows the immune system to recognize bacterial polysaccharides. In addition, it regulates expression of the cathelicidin and b-antimicrobial peptides (AMPs), which play vital roles in targeting intracellular pathogens. Thus, any microbe capable of dysregulating VDR activity would significantly disable the innate immune response, facilitating its persistence. Indeed, several of the pathogens most often linked to inflammatory disease have in fact evolved to survive in exactly this fashion. Persistent M. tuberculosis has evolved to slow VDR activity. When lymphoblastoid cell lines are infected with EBV, activity of the VDR is downregulated as much as 15 times. Mycobacterium leprae, cytomegalovirus, and Borrelia burgdorferi also inhibit VDR activity to varying degrees. The fungus Aspergillus fumigatus, common in cystic fibrosis, secretes a gliotoxin that significantly downregulates VDR expression. In addition, bacterial species in biofilm often secrete the sulphonolipid capnine, which we have demonstrated can inhibit VDR activation. Indeed, disabling the innate immune response via the VDR pathway is such a logical pathogen survival mechanism that many more species capable of persisting in the same or similar fashion will likely be identified in the coming years."


Interestingly, if I'm not mistaken, in case of hyperosmolarity there is no need for activation of the VDR for LL-37 secretion :

Osmolality controls the expression of cathelicidin antimicrobial peptide (LL-37) in human macrophages (https://www.biorxiv.org/content/10.1101/332635v1):
"An imbalance between extracellular and intracellular fluid osmolality causes osmotic stress and affects cellular homeostasis. Recent research suggests that osmotic stress is also associated with various innate and adaptive immune responses. Here we present the surprising finding that osmolality tightly controls the expression of cathelicidin antimicrobial peptide (CAMP) in human macrophages. CAMP expression is strongly upregulated under hyperosmotic conditions and downregulated under hypoosmotic conditions. We also provide evidence that this osmolality-mediated antimicrobial response is dependent on nuclear factor of activated T-cells 5 (NFAT5) and mitogen-activated protein kinase (MAPK) p38. Finally, Toll-like receptor (TLR) activation inhibits osmolality-mediated expression of CAMP in human macrophages, suggesting that this osmolality-dependent regulation of CAMP is more relevant under homeostatic conditions, rather than during acute infections. This study expands our knowledge of the regulation of human antimicrobial peptides and highlights osmolality as an important and independent factor shaping host innate immune homeostasis."
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