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HBsAg Inhibits IFN-α Production in Dendritic cells

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0044900

HBsAg Inhibits IFN-α Production in Plasmacytoid Dendritic Cells through TNF-α and IL-10 Induction in Monocytes

abstract (full article in the link)
Type I Interferon (IFN) is one of the first lines of defense against viral infection. Plasmacytoid dendritic cells (pDCs) are professional IFN-α-producing cells that play an important role in the antiviral immune response. Previous studies have reported that IFN-α production is impaired in chronic hepatitis B (CHB) patients. However, the mechanisms underlying the impairment in IFN-α production are not fully understood. Here, we report that plasma-derived hepatitis B surface antigen (HBsAg) and HBsAg expressed in CHO cells can significantly inhibit toll like receptor (TLR) 9-mediated Interferon-α (IFN-α) production in peripheral blood mononuclear cells (PBMCs) from healthy donors. Further analysis indicated that monocytes participate in the inhibitory effect of HBsAg on pDCs through the secretion of TNF-α and IL-10. Furthermore, TLR9 expression on pDCs was down-regulated by TNF-α, IL-10 and HBsAg treatment. This down-regulation may partially explain the inhibition of IFN-α production in pDCs. In conclusion, we determined that HBsAg inhibited the production of IFN-α by pDCs through the induction of monocytes that secreted TNF-α and IL-10 and through the down-regulation of TLR9 expression on pDCs. These data may aid in the development of effective antiviral treatments and lead to the immune control of the viral infections.
12 Responses
Avatar universal
How the differences in the glycosylation and lipid content affect the function of HBsAg also requires further study.

The activation of pDCs leading to the production of IFN-α is important for an effective anti-HBV immune response. Our present study reported that HBsAg acted on pDCs in an indirect manner by inducing monocytes to secrete TNF-α and IL-10, which mediated the inhibition of IFN-α production by pDCs. With the new understanding of the relationship between HBsAg, monocytes, pDCs and the cytokine response, our study has provided a novel insight into the complicated mechanism by which HBV modulates the innate immune system. These data will help to further understanding how HBV establishes persistent infection and which may aid in the development of an effective antiviral treatment to the control of HBV infection.
Avatar universal
it would be very interesting to see how simvastatin can affect lipid content of hbsag and how intf affects lipid content of hbsag....
my guess is lowering of intracellular and serum cholesterol may reduce lipid content of hbsag and impair some of these inhibiotry pathways on dc and monocytes

of course modyfing lipid will not clear any infection but may boost some immune response
Avatar universal
Stef,

Now you see how the right the soviet doctors were about all this. That is why if they were catching people early with acute HepB they put them in the hospital and gave them interferon infections. Especially to those that had a weak immune response, and put people on IV's. 30 or 40 days after people could forget about HBV.

Now that in Russia is passive treatment is endorsed chronicity of HBV has tripped. Because there are also doctors that get paid by Gilead and others to prescribe us what most of don't really need unless we are in very advance stages of the disease..

Now with the progression of science they are able to understand the exact kinetics as to why HBV gets chronic.. for which they only had theories about back then.

So what we need is more medications that lower the surface antigen itself. And something to rescue the immune system, it may actually come alive with surface antigen lowered. But the point is interferon is key here..As well as the surface antigen test, that is not available in some countries...

Which also proves that we really have no need for such a wide use of nuclear side analogs.

You think US drug companies and research doctors with all their high tech tools were not aware of all along ? :)

I think we start seeing all this info pop up here and there because they are getting ready to release better drugs, but not now rather in 2017-18..


And  I also think we need to demand these drugs now.  They made HBV too big of a problem then it really is to make money on it.

Look at the HIV treatment. People were fed all that AART therapy.. with the end result still death.. When in fact a bone marrow transplant cures HIV... Something that is still not being discussed widely.

In Japan they they were treating symptomatic cases of HTLV with a bones marrow transplant since long ago.. with like 99% success rate. And HIV is about 90% same virus as HTLV. Moral of the story profit and medicine do not go together.
Avatar universal
[quote]
it would be very interesting to see how simvastatin can affect lipid content of hbsag and how intf affects lipid content of hbsag....
my guess is lowering of intracellular and serum cholesterol may reduce lipid content of hbsag and impair some of these inhibiotry pathways on dc and monocytes

of course modyfing lipid will not clear any infection but may boost some immune response [/quote]

that is why Interferon + Symvastatin worked so well for one guy here.
Avatar universal
Good points on the lipids and I think you are right. But where to find clinics that will be willing to try all this?
Avatar universal
another question is:

will imiquimod reactivate dentritic cells
will imiquimod improve intf response by using imiquimod+int?

imiquimod+local intf injections is used already on HPV infections
Avatar universal
Well if Gish said it will be the last  medicine we take he must know something.

I wish they do better clinical trials. So frustrating all this.
Avatar universal

well that is gilead vice president you can t really ask him anything which is gilead competitor....
Avatar universal
:) where did you hear this?  I read that he is a consultant that gets grants and research money from the big three drug companies. He is a good man  and could have helped many people. But here in the US drug companies fund  and steer the research the way they want to. Instead of the government providing the funds for research so doctors like dr. Gish could use what is available.

In the end result the patient here looses. From one side it is the drug companies control cure developments from many illnesses from the other it is the US medical insurance mafia that decides and tells the doctors how and with what to treat a patient and what tests to give a person.
So they can totally chose to not test you till you develop cancer and die.

So it is a total ganster system here taken over by the corporate interest that lobbies and buys this basically from politicians to make all this legal.

So really sick people like us cant really fully benefit from the likes of dr.Gish and what they know and are capable of doing.  

And that is the main problem people. We US patients take all this silently; accepting this  anti human system that ultimately softly kills us. And it happens with all the serious diseases not with just hep b. Patients here get the raw deal. Even people with good health insurance are getting it.

it is a total bedlam Stefan I tell ya. All they do here for us is either Tenofovir; entecavir; and very rarely interferon. So they do only what is approved by FDA And what health insurance will cover. So what is good for patient is being totally ignored.

And what is extremely frustrating is knowing the fact  that with the right combo treatments available today they can help us loose this surface antigen in 50% of the cases maybe even more if they treat people early with interferons. And it is frustrating that it happens in America that usually leads the world with pioneering technology. And the know how is there. Look at the research papers people like dr.Gish write.

But it happens because the drug companies here are controlling the research and the direction cure developments go. They know very well that in very few countries now they can pull the money needed to bring to market drugs that not just treat the disease but cure it.

And as far as FDA goes I really dont know what good they do. They choose not to regulate the supplement industry completely that sell sometimes very highly questionable products. And yet when it comes to HBV for example they dont approve known medications that help us and treatments that work.  
It is  frustrating ..,
Avatar universal
To make a point with all this we really need hep b treatment centers somewhere in the world that would use the technologies and  treatment know how that are available today. With funding coming from the patients.  

Because are interests as patients are totally not being cared for and looked after.

Yes it is a big hope for us to see how Myrcludex will do in Russia. And how that company Hepatera will go about distributing this medication and access to it for patients.
Avatar universal

other researchers told me this, dont know if they meant:
he is so influent as if he was vice president or actually is vice president...

anyway since imiquimod and gs9620 are so similar chemically, and since gilead didn t answer the specific question at conference on gs9620:

" is gs9620 similar to other trl7 agonists on the market"
answer: we are not allowed to comment on this.....

that is a question you cannot ask them, obviously
Avatar universal
VB

Do you have any info on the Soviet tactic of Inf for acute?

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