The immunomodulatory effects of HIV on dendritic cells and their activation of the T cell response

My research is in the area of immunovirology, specifically HIV research with focus on the immunomodulatory effect this virus has on dendritic cells and T cells. 

I have also ongoing projects exploring new adjuvants and vaccine constellations for cancer and virus. Furthermore, I am investigating the induction and sustainment of cancer associated inflammation and the deleterious effect this has on host immune defense.

Immunomodulatory effects of HIV-1’s interactions with DCs and T cells from blood and mucosa

HIV virusHIV virus. HIV is a retrovirus that infects CD4 T cells and dendritic cells, and breaks down the host immune system, leading to AIDS.
So far over 30 million people have died from HIV-1 infection (figure 1), the majority of them in the developing countries, and this epidemic is still cause for major concern. 

The existing antiretroviral therapy dampens the infection and the destruction of the immune system, i.e. AIDS, but does not cure the disease. Sadly, this therapy is not available to all HIV infected and is a very expensive lifelong commitment with severe side effects.

A vaccine blocking HIV infection is the Dendritic cell sought-after solution but there is no hope that we will have such a vaccine in the near future. Instead we can hope for a therapy that induces a potent long lasting immune response consisting of CD4+ and CD8+ T cells, two types of control cells involved in the immune defense, that have proven to be important to control the infection.

Dendritisk cellHIV virus. HIV is a retrovirus that infects CD4 T cells and dendritic cells, and breaks down the host immune system, leading to AIDS. There exists a unique cell in all tissues in our bodies, the dendritic cell (DC) (Figure 2) with unique ability to activate T cells so they can perform their job in the body. DCs in the vaginal and rectal tissues are one of the first cells to encounter HIV during intercourse with an infected individual (Figure 3 and 4).

Unfortunately, HIV hijacks the DCs, which makes this cell responsible for spreading the virus to interacting T cells in the body which provokes HIV-infection of T cells and cell death when it should be initiating immune responses to fight the infection.

My research aspires to elucidate the mechanisms behind the immunomodulatory effects HIV exerts on DCs and on their ability to activate T cells. Focus will be on; Elucidation of the mechanisms involved in HIV’s binding to and uptake by DCs and the subsequent degradation that leads to DC antigen presentation of HIV peptides for activation of HIV specific T cells. Elucidation of the mechanisms responsible for the negative effects HIV exerts on DCs and if presence of HIV virions during DC T cell priming impairs the T cell function.

Elucidate the effect opsonized HIV-1 exerts on immune cells such as DCs, NK cells and T cells. Identification of receptors and cells involved in the initial HIV infection of cervical mucosa and colorectal mucosa, and potential microbiocides that can block the initial infection, and elucidation of why HIV affects the T cells in the gut to a higher extent than the T cells in blood.

HIV will continue to kill people and have a great impact on mankind until we have a drug that can stop this infection. My ambition is that the planed research will answer some basic questions regarding the role of DCs in HIV pathogenesis and induction of potent immune response against this virus. This knowledge will guide how a vaccine/therapy needs to be constructed in order to have high efficacy.

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Dendritisk cell och HIVDendritic cells and HIV. Confocal image of dendritic cells (red surfaces and blue nucleai) which have internalised HIV virions (green/yellow).
Mucosal transmissionDendritic cells - key players during HIV infection. Dendritic cells are the first cells to interact with HIV during sexual transmission of the virus. While they are vital for the induction of HIV-specific immune responses, they also transfer HIV to CD4 T cells in the mucosa and lymph nodes, aiding in establishment of systematic HIV infection.
Dendritiska celler i slemhinnaDendritic cells in mucosa. Image of cervical tissue taken with a confocal microscope. Cell nucleai dyed blue, and dendritic cells red. The arrow indicates HIV virions (green) close to a dendritic cell.

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