Capnine
Part of the theory of the pathogenesis of chronic inflammation is that intracellular bacteria disable a crucial part of the innate immune system, the Vitamin D Receptor (VDR) located in the nucleus of phagocytes. It is theorized they do this by producing substances (perhaps capnine) that prevent the VDR from producing anti-microbial peptides such as cathelicidin, which kill invading pathogens. Thus, intracellular bacteria are allowed to multiply, and also inhibit a number of other important functions the VDR would normally perform. In theory, these bacterial ligands also induce the phagocytes to release Th1 cytokines which cause Th1/Th17 inflammatory symptoms.
This theory was inspired by the gliding bacteria discovered in a study of infected prosthetic hip joints. [1] Gliding bacteria live in biofilms and the gliding motion is associated with a unique lipid called capnine. Computer modeling of capnine was done by one investigator who concluded that capnine is a strong inhibitor (antagonist) of VDR transcriptional activity. Citing a study of sulfonolipids of gliding bacteria [2] he posited that pleomorphic intracellular bacteria also produce substances that inhibit VDR actions.
A 2007 study by University of Washington researchers lends credence to this theory because it confirms that bacteria that live in biofilms (like the gliding bacteria) can be found inside cells and "biofilm formation is generally an important strategy bacteria use to evade host responses and antibiotic therapies." [3]
These researchers "...found bacteria could establish residence inside cells involving several behavioral changes that allow the bacteria to form cooperative communities known as biofilms. By working together, bacteria in biofilms build themselves into structures that are more firmly anchored in infected cells and are more resistant to immune system assaults and antibiotic treatments."
This study found more evidence of intracellular biofilms. "The possibility of bacterial ReA triggers to enter the cell wall-deficient state and to persist in bacterial biofilms, and evidence, suggesting that cell wall-deficient bacteria and bacterial biofilms are involved in the foci of chronic infection [4] These researchers suggest that intracellular bacteria form biofilm pods. [5]
Recently, Japanese researchers have demonstrated the ability of one intracellular bacterial species to subvert natural processes and evade detection by the immune system. They discovered that Anaplasma phagocytophilum (Ap) secrete a protein which binds with another protein produced by white blood cells; and that connection creates compartments that siphon host-cell nutrients to feed the bacteria, enabling their growth inside the white blood cells.
Their report states: "All of this activity allows the bacteria to remain hidden from the immune system because the induction of autophagy is considered a normal cell function and it does not produce any inflammation, which would recruit infection-fighters to the scene. Instead, the Ap bacteria set themselves up comfortably inside granulocytes and steadily grow for a few days until they rupture their host cells and generate a strong immune response -- which makes an infected person sick." [6]
Although the capnine computer modeling has not been corroborated, these studies lend credence to the theory that intracellular, cell-wall-deficient bacteria have developed ways of thwarting the immune system (e.g., secretion of ligands to down-regulate the VDR).
[1] Identification of bacteria on the surface of clinically infected and non-infected prosthetic hip joints removed during revision arthroplasties by 16S rRNA gene sequencing and microbiological culture.
Dempsey KE, Riggio MP, Lennon A, Hannah VE, Ramage G, Allan D, Bagg J.
Arthritis Res Ther. 2007;9(3):R46.
[2] Sulfonolipids of gliding bacteria. Structure of the N-acylaminosulfonates.
Godchaux W 3rd, Leadbetter ER.
J Biol Chem. 1984 Mar 10;259(5):2982-90.
[3] Detection of Intracellular Bacterial Communities in Human Urinary Tract Infection.
David A. Rosen, et al
PLOS Medicine, December 2007
[4] New insights into bacterial persistence in reactive arthritis.
Astrauskiene D, Bernotiene E.
Department of Rheumatology, Institute of Experimental and Clinical Medicine at Vilnius University, Lithuania
[5] Multi-species bacterial biofilm and intracellular infection in otitis media.
Ruth B Thornton, et al
BMC Pediatr. 2011; 11: 94.
[6] Inaugural Article: Autophagosomes induced by a bacterial Beclin 1 binding protein facilitate obligatory intracellular infection.
H. Niu, Q. Xiong, A. Yamamoto, M. Hayashi-Nishino, Y. Rikihisa.
Proceedings of the National Academy of Sciences, 2012; DOI: 10.1073/pnas.121867410
