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Source: Immunology Research  May 11, 2020  3 years ago
BREAKING! Immunology Research: Medical Scientists Discover New Dendritic Immune Cells That Could Also Be Targeted For COVID-19 Treatments
BREAKING! Immunology Research: Medical Scientists Discover New Dendritic Immune Cells That Could Also Be Targeted For COVID-19 Treatments
Source: Immunology Research  May 11, 2020  3 years ago
Immunology Research: Medical researchers and immunology experts from VIB Life Sciences Research Institute in Belgium have made a major significant discovery of a new type of antigen-presenting immune cells.

The research by some of the world’s most renowned  medical scientists including the teams of Dr Bart Lambrecht, Dr Martin Guilliams, Dr Hamida Hammad, and Dr Charlotte Scott all from the VIB-UGent Center for Inflammation Research will basically lead to textbooks on immunology being rewritten with the discovery of these new immune cells, that are part of an expanding family of dendritic cells, that play critical roles presenting antigens to other immune cells during respiratory virus infections. The research findings could explain how convalescent plasma helps to boost immune responses in virus-infected patients. https://www.cell.com/immunity/pdf/S1074-7613(20)30163-1.pdf

Typically when human bodies face an infection, it responds with inflammation and fever. This is a sign that the immune system is working, and leads to the activation of many cells, like soldiers in an army.
Importantly, dendritic cells (DCs) are the ‘generals of that army’. They can precisely activate and instruct the ‘soldiers’ to kill infected cells by presenting antigens derived from the ‘invaders’ to cells of the immune system.

To date, there are several types of dendritic cells (DCs) that perform antigen-presenting functions in the body.
A main type of conventional dendritic cells continuously scans the body for dangerous invaders, even when there is no infection. When there is inflammation triggered by infection, another subset of DCs emerges from inflammatory monocytes. Because monocyte-derived DCs are easily prepared in vitro from monocytes isolated form human blood, it was always assumed these cells were very important antigen-presenting cells. Clinical trials using monocyte-derived DCs in cancer therapy have however been disappointing.    
This new research shows that monocyte-derived dendritic cells are poor antigen-presenting cells, but have wrongly been assumed to have these functions because of a case of mistaken identity.
The researchers studied rodent models with a viral respiratory infection (pneumonia virus of mice and influenza virus) with single-cell technologies.
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This single-cell resolution allowed them to finely separate the monocyte-derived cells from other DCs during their response to the infection. They found that monocyte-derived DCs do exist, but actually do not present antigens. The reason for all the confusion in the past is that a look-alike new DC emerges which is called inflammatory type 2 conventional DC, or inf-cDC2 , that combines some of the best characteristics of monocytes, macrophages, and conventional DCs, to induce the best form of immunity. 
< br /> Dr Lambrecht told Thailand Medical News, “This was a major surprise for us. We have all been taught that monocyte-derived cells are excellent antigen presenting cells, certainly when there is an inflammation. Now, we show that it’s actually a new hybrid DC type that’s doing all the work. This really changes what we know about the immune system and is very important knowledge for understanding respiratory viral infections and other inflammatory diseases.”

“It took a massive team effort but the strength of single-cell sequencing has finally cracked the complex DC code. Many contradicting findings from the last two decades now make much more sense. This also opens tremendous therapeutic opportunities, since vaccination strategies can now be designed to trigger formation of inf-cDC2s and thus generate a stronger antiviral immune response.”said Dr Guillaims.

Dr Scott who is part of the team also commented, “Through the use of single cell technologies we have been able to align all the research findings from the past few years and identify the distinct cell types involved. Moving forward it will be very interesting to see under what other inflammatory conditions these inf-cDC2s are generated and how they can potentially be targeted therapeutically.”
The study findings of the team also have a direct relevance for the current COVID-19 pandemic, caused by the SARS-CoV-2Coronavirus. An emergency treatment that is currently being explored is the use of convalescent plasma, or the blood plasma of recovered patients.  

Lead author of the new research, Dr Cedric Bosteels said, “One of the unique features of the new DCs is that they express functional Fc receptors for antibodies that are found in the plasma of patients who have recovered from COVID-19.”

This research is the first to demonstrate that one of the mechanisms through which convalescent plasma and the virus-specific antibodies in it work, is via boosting of inf-cDC2. Since boosted DCs induce a much stronger immune response.
Hence this study finding reveals a new target for therapeutic intervention for viral infections and other inflammatory diseases.
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