Deciphering the mechanisms of NK and B cell dysfunction in Chronic Hepatitis B patients

What can be the direct consequences of an hepatitis B infection?

Hepatitis B, which is prominent worldwide with at least 254 million known carriers, is an agent inducing/promoting more carcinoma cases along with weakening immune response (inhibition of the immune system by HBV

What mechanisms, in the immune system become deficient following an HBV chronicity?

• Production of type I dendritic cells (DCs)

• Antibody production by B cells (B cell dysfunctionality)

• T cell – exhaustion

• NK cell dysfunction, exhaustion

• Macrophages

What are the main roles of B cells? What mechanisms are activated in response to microbial DNA?

Produce antibodies, create long term memory, present antigens to help and activate T cells, refine antibodies by going through somatic hypermutation.

TLR9 (intracellular recognizing non methylated DNA) stimulation enhances B cell activation, proliferation, and function, especially in response to microbial DNA (like viral or bacterial) → NFkB

What happens to TLR9 in patient with HBV? And what about in chronic HB infections?

Many oncoviruses, like HPV can block TLR9 so does HBV → seems to inhibit CREB which is a is a transcription factor is expressed in B cells that when phosphorylation to regulate the transcription of TLR9.

In HB patient, TLR9 expression went down in all B cells (naive and plasma cells).

What happens to NK cells, in infected patients? Give 2 examples of down regulated genes and how the inhibition occurs

Upregulation of the expression of immune checkpoints proteins along with a decrease in NK cells metabolism.

mTOR and PARP9 → essential for NK cells to induce phosphorylation of S6 (pS6), linking it to mTORC1 activation

The inhibition may occur via ADP-ribosylation, a process potentially involving PARP9 or related pathways