Apoptosis sensing receptors protect brain from virus invasion

The TAM receptors, Tyro3, Axl, and Mertk, and their ligands, Gas6 and Protein S, are essential for the efficient phagocytosis of apoptotic cells. In the immune system, they act as inhibitors of the innate inflammatory response to pathogens. It was hypothesized that deletion of TAM receptors in dendritic cells could improve anti-viral immunity.  

Unexpectedly, however, new study from Nature Medicine showed that deletion of TAM receptors increased mice susceptibility to neurotropic viruses by its effect on blood-brain barrier (BBB).

Due to complex nature of TAM receptors biology, I am reviewing this paper as an example of "surprising finding" rather than an example of definite proof of concept. I will just quickly go through more or less straightforward findings of this paper. 

First, the authors found that TAM receptor deletion made mice highly susceptible to West Nile virus (WNV) subQ infection (no difference were seen for viral pfu/g with direct intra-brain infection). 

Next, TAM deficient mice were also susceptible to another neurotropic virus, La Crosse virus (LACV).

Finally, the authors showed that TAM receptor deficiency increased BBB permeability.

In summary, the results from this study were unexpected. The authors pointed out that development of TAM inhibitors (e.g. clinicaltrials.gov ID:NCT00605618) could be affected by these findings.

David Usharauli