Fondation Merieux

A family foundation dedicated to fighting infectious diseases

Mechanisms behind chronic infections (TB, HBV, HIV…): molecular and cellular mechanisms, evasion mechanisms, immunity

2 - 4 May 2016, Les Pensières, Annecy (France)

When a pathogenic microorganism infects the human body, a dramatic activation of the innate and adaptive immune response occurs. In most cases, the interaction between the immune system and the pathogen result in clearance of the infection. However, some pathogens are capable of maintaining their presence, despite the severe attacks of the immune system, giving rise to persistent infection.

To remain and survive for a long period of time in its host, sometimes lifelong, the pathogens have evolved a range of elaborate immune-evasion strategies which may involve (1) hiding from the immune system, (2) interfering with the function of the immune system and/or (3) exploiting the immune system for their own benefit.

Many herpes viruses hide from the immune system by entering into a state known as latency in which the virus does not replicate. No viral proteins or peptides are presented on the surface of the infected cells and the cells cannot be eliminated. Other viruses, like VZV, invade neurons, which carry very little MHC I class molecules making it hard for the CD8 T cells to recognize infected cells.

Certain pathogens interfere with the cells of the immune system to block or dampen its actions. There are similarities in the immuno-modulatory mechanisms used by viruses and bacteria that have to overcome the same host immune system. Indeed, both classes of pathogens can inhibit complement, inhibit cytokines, interfere with TLRs, and block acquired immunity allowing long-term survival.

Pathogens can also exploit immune cells for their own benefit. This mechanism is demonstrated by HIV that replicates in CD4 T cells, EBV in B cells, and Dengue virus that infects Langerhans cells. Another example is M. tuberculosis which is taken up by macrophages but prevents the fusion of the phagosome with the lysosome, protecting itself from the bactericidal actions of the lysosomal contents./p>

This workshop will focus on immune-evasion strategies employed by three pathogens that are responsible for a very high medical burden, namely, tuberculosis, HIV and Hepatitis B infection. We will discuss the current understanding how these pathogens employ evasion mechanisms, and how to translate this knowledge to the development and rational design of new medicines and therapeutic vaccines.

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