Sunday, October 2, 2011

IL-6: one more time, please ?!

Chronic infections represent a special challenge to the adaptive immune system. It would not be an exaggeration to say that essentially what we know about how an adaptive immune system normally functions is entirely based on research or clinical observation related to the acute infections. Chronic infection develops in situations when adaptive immune system is not capable of complete or near complete elimination of invader-pathogen. In this scenario, invader-pathogen persists long-term, slowly spreading, infecting healthy cells. At this point adaptive immune system faces a difficult choice: if it kills all infected cells then the tissue and body will not survive because this will cause too much damage (so called immune pathology). Only alternative solution for adaptive immune system (to T and B cells) is to switch to the “damage-control” mode, where the focus will be containment, not elimination. This will require new pathway of effector differentiation that causes minimal damage to the infected tissues.

If you are interested to know what kind of modifications are happening to adaptive immune system during chronic infections, I recommend to read the following article recently published in Science (1). In this paper by James Harker et al, the focus is on the mouse model of chronic viral infection, specifically LCMV clone 13. The first (and in my opinion only) interesting observation they made was how IL-6 expression changes during clone 13 infection. Unlike acute infection, clone 13 produces two peaks of IL-6: early (at day 1-3) and late (at day 25). This late peak of IL-6 is primarily derived from irradiation-resistant follicular dendritic cells (FDCs). The authors do not go beyond this simple observation to explain how this is happening. Furthermore, for some reason, they are totally neglecting to discuss another cytokine, G-CSF that similar to IL-6 also had biphasic expression and may play independent role in protection during chronic infection. The rest of the article is mainly supporting data (more or less already known), for example, showing how IL-6 influences T follicular helper cell development, that in turn affects virus-specific antibody production level and its affinity (while earlier studies mainly ignored the role of B cells or antibodies played during LCMV infection, the more recent research clearly shows that at least for clone 13 infection antibody-dependent protection is essential (2).

Such prominent role of IL-6 in protection against chronic infection as this article shows is supported by other independent observation. For examples, an article published in Cell showed that IL-7, another cytokine, has protective effect during clone 13 infection and this effect was dependent on IL-6 (3).

David Usharauli

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