Tuesday, November 18, 2014

Flu detour

Influenza virus, commonly called Flu virus, has a volatile nature. There is, of course, Flu vaccines available in the market, but their efficacy are surprisingly barely 70%. 

Now, Flu virus infects upper and lower respiratory tissues, mainly epithelial cells. So clinical symptoms are usually proportional to the degree of tissue damage along the respiratory tract. However, in some individuals, Flu causes additional GI tract issues. Why is that?

New study in JEM may provide some new insight. It is important to point out at this stage that this study has examined a mouse model of Flu infection.

Initially, the authors observed that infection of mice with PR8, a mouse-adapted Flu strain, caused their weight loss and moderate diarrhea.

Interestingly, examination of GI tract for virus presence showed that unlike lung tissue, Flu virus did not infect GI tract directly. So why were the mice getting diarrhea?

IL-17 has been implicated for some time now in GI tract tissue damage. Indeed, infection of IL-17A-KO mice with Flu virus caused little or no intestinal tissue damage. Similar result was obtained when using anti-IL-17 antibody injections.

Since lung tissue damage was similar in both wild-type and IL-17-KO mice, the authors focused on IFN-gamma expression. Interestingly, IFN-gamma-KO mice also showed minimal intestinal damage.

Additional experiments showed Flu infection in mice induced high level expression of CCL25 in intestinal tissue and its blocking via anti-CCL25 treatment abolished intestine damage.
Other set of experiments indicated that Flu infection modified gut microflora composition by its effect on IFN-gamma expressing T cells which migrated from lung to intestinal tissue CCL25 dependent-manner. This changes in gut microflora was associated with local tissue damage in IL-15 and IL-17 manner.

It my opinion this study initially generated a clear data but as it progressed Flu model became more complex and at times confusing. For example, no data are presented of the level of lung tissue damage in IFN-gamma KO mice. It is not clear either whether IFN-gamma induces gut barrier damage and IL-17 production or vice versa.

David Usharauli

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