Thursday, December 4, 2014

Great illusion: helminth-virus co-infection

This is a second paper in a series that examined the effect of co-infection on body's immune response. 

This one came from David Artis' lab (though both papers have another senior author H.W. Virgin, who by the way has just published another two papers in journal Science).

David Artis is a quite prolific scientist in immunology. This paper is well done indeed. Simple and complete. That's why it was accepted for publication in Science within 1 month of submission (a quite an achievement :)

Initial data showed that both CD8 and CD4 T cell responses to mouse norovirus were diminished in presence of Trichinella Spiralis larvae (TH2 activator). 
Not just overall magnitude of anti-viral CD8 T cell response was reduced but even CD8 T cell poly-functionality and CD4 T cell response were impaired in presence of Trichinella infection. In addition, helminth infection led to increase in viral replication in the gut
This reduction of anti-viral immune response were observed in studies using a different virus, Flu virus expressing LCMV gp 33 protein and a different helminth infection (Hp)
Furthermore, this modulation of anti-viral T cells response and viral replication by helminth were apparent even in germ-free mice, indicating that it was gut microbiome independent process. 
Mechanistically, this modulation of viral immunity by helminth was mediated through STAT6 and IL-4ralpha and TH2 signature molecule Ym1 (I will call it ya-me 1). 
In summary, this paper clearly and unequivocally showed that helminth (worm) co-infection diminishes anti-viral T cell response and as a consequence promotes viral replication in target tissue.

In my opinion, this paper is great but has totally missed one critical point. It absolutely does not matter how much helminth infection affects the particular readout of immune response measured or how much it promotes viral replication, unless one shows that this modulation has any detrimental biological effect on the host. however, both papers failed to provide any guide as to the measure of tissue pathology (did increase in viral replication cause more tissue damage? What about antibody response?). Without such information, however, the data are just nice but irrelevant.

David Usharauli



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