Blocking the VDR

Capnine is a protein created by bacteria, a protein which may bind to and antagonize (inactivate) the VDR. The secretion of capnine and substances like it fulfills an important evolutionary need for bacteria: to disrupt the innate immune response.

In the arms race of host–microbe co-evolution, successful microbial pathogens have evolved ingenious ways to evade host immune responses.¹³

Studies have indicated that the dysregulation of VDR may lead to exaggerated inflammatory responses, raising the possibility that defects in Vitamin D and VDR signaling transduction may be linked to bacterial infection and chronic inflammation. Further characterization of Vitamin D/VDR will help elucidate the pathogenesis of various human diseases and in the design of new approaches for prevention and treatment.Jun Sun ¹⁴

Since the VDR is at the heart of the innate immune system, bacteria can survive by discovering how to disable it through a variety of different actions. Actions accumulate and are more powerful than individual actions.

In keeping with evolutionary theory, a growing number of substances and species have been shown to downregulate the activity of the VDR:

• Borrelia burgdorferi – Live Borrelia burgdorferi reduced VDR expression in monocytes (phagocytes) by 50 times, and lysates (“dead” Borrelia) reduced it by 8 times¹⁵
• Mycobacterium tuberculosis – shown to downregulate the VDR 3.3-fold ¹⁶ which makes sense given that an active VDR helps phagocytes to suppress the intracellular growth of M. tuberculosis ^17 18
• “Gliding” biofilm bacteria have been shown to create Capnine – Capnine is a 2-amino-3-hydroxy-15-methylhexadecane-1-sulfonic acid, and is created by the generaCytophaga, Capnocytophaga, Sporocytophaga, and Flexibacter.^19 20 The secretion of capnine meets an important evolutionary need for bacteria. Capnine possesses a high affinity for the VDR as evidenced by the fact that molecular modeling shows that its stable in the ligand binding pocket. Molecular modeling further shows that when capnine is docked in the VDR, it inactivates the receptor.
• Chlamydia trachomatis – shown to downregulate the VDR in unpublished work

The following substances reduce the number of VDR, without which immune function is limited:

• Caspase-3 – A protein which cleaves (breaks apart) the VDR structure and thus limits the ability of VDR to perform gene transcription.²¹ The caspases are upregulated by Shigella infection,²² which implies that the VDR may have a faster cycle time in disease than in health.

According to the Marshall Pathogenesis, pathogens’ production of ligands, which bind to and antagonize (inactivate) the Vitamin D Receptor, is one of the fundamental processes by which chronic inflammatory disease occurs. The consumption of other immunosuppressive substances also has an effect.

http://mpkb.org/home/pathogenesis/vitamind/metabolism