Immunity system complexity: how chlamydia escapes detection (Introduction)

by David Turell , Thursday, February 23, 2023, 18:12 (429 days ago) @ David Turell

Cloaking and a specialized protein:

https://www.the-scientist.com/the-literature/how-chlamydia-guards-itself-against-the-im...

"Coers has spent years figuring out how Chlamydia trachomatis, the causative bacterium in humans, evades destruction. In a recent study, Coers and his team discovered a key protein that allows C. trachomatis to slip past the body’s defenses.

"To enter a host cell, Chlamydia cloaks itself in a piece of the host cell’s membrane, forming a vacuole, or inclusion, where it grows and divides uninterrupted by immune cells. T cells can detect Chlamydia in the brief time it lives outside the cell and, in response, release gamma interferon (IFN-γ), an inflammatory cytokine that triggers destruction of the pathogen. But something about the inclusion allows Chlamydia to hide from the immune response and persist for months or years.

***

"The team performed a genetic screen of various mutated C. trachomatis strains grown inside human epithelial cells in the presence and absence of IFN-γ. The C. trachomatis strains most susceptible to IFN-γ-mediated destruction had mutations in a gene that encodes a protein the researchers named GarD (formerly CTL0390), indicating that GarD is important for C. trachomatis’s survival. Imaging experiments on IFN-γ-resistant C. trachomatis strains revealed that GarD blocks ubiquitin binding by inserting itself into the inclusion membrane. Disabling GarD allowed ubiquitin binding and left the bacteria vulnerable. Meanwhile, mice defend themselves from rodent-infecting C. muridarum by blocking ubiquitin via a different mechanism entirely.

“'When the GarD protein is there, the inclusion . . . disguises itself, like an invisibility cloak from Harry Potter,” Coers explains. “Now we understand why interferon-γ is not able to clear infections and why these infections last for such a long time.”

“'I think it’s an important and reliable result,” says Bob Brunham, an infectious disease scientist and professor emeritus at the University of British Columbia who was not involved in the study. “It shows just how evasive Chlamydia is.”

"The researchers also discovered that IFN-γ activates a protein called mysterin (also called RNF213) that’s responsible for attaching ubiquitin to the inclusion, though Coers notes that how exactly GarD prevents mysterin from doing so remains, aptly, a mystery."

Comment: either Chlamydia invented the protective molecule or it appeared by luck. Would God have been involved? I don't know. All unknowns