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Flu virus induces gut immune injury via microbiota-mediated Th17 cells

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natasa778

Senior Member
Messages
1,774
http://jem.rupress.org/content/early/2014/10/28/jem.20140625

... We explored the occurrence of gastroenteritis-like symptoms using a mouse model of respiratory influenza infection. We found that respiratory influenza infection caused intestinal injury when lung injury occurred, which was not due to direct intestinal viral infection. Influenza infection altered the intestinal microbiota composition, which was mediated by IFN-γ produced by lung-derived CCR9+CD4+ T cells recruited into the small intestine. Th17 cells markedly increased in the small intestine after PR8 infection, and neutralizing IL-17A reduced intestinal injury. Moreover, antibiotic depletion of intestinal microbiota reduced IL-17A production and attenuated influenza-caused intestinal injury. Further study showed that the alteration of intestinal microbiota significantly stimulated IL-15 production from intestinal epithelial cells, which subsequently promoted Th17 cell polarization in the small intestine in situ. Thus, our findings provide new insights into an undescribed mechanism by which respiratory influenza infection causes intestinal disease.
 
halcyon

halcyon

Senior Member
Messages
2,482
Pretty interesting. Tissue damage due to Th17 action seems to be a definite thing. @Hip linked me to this paper recently showing that induced Th17 action by Coxsackie virus increased myocardial replication and damage.
 
anciendaze

anciendaze

Senior Member
Messages
1,841
Just a caution: although this is talking about immune activity which is very well documented there is still a problem of specificity. Th17 and IL-17 are part of a very general response to a wide range of infections, and all humans are infected with a variety of microbes we generally tolerate. There was a paper some years ago speculating about the meaning of this signal which had "the danger is growing" in its title. That still seems like a good way to interpret these signals.

What I believe I'm seeing is that some pathogens redirect immune response to protect themselves (talking, for convenience only, as if they knew what they were doing.) This causes the general response to be directed at commensal microbes which are either harmless or beneficial. Some of these microbes attack pathogens like bacteria in the gut which are a real danger to life. They are our allies in the constant fight for survival. The result of a mistaken attack on such microbes is a proliferation of the real pathogens they attack.

None of this tells us much of anything about the pathogen which started the process. It has successfully protected itself from immune response by convincing the immune system there is a phantom threat due to something entirely different. (Sounds like a political tactic some humans have used.) As a result the immune system develops tolerance for the true pathogen, and antibody response to that microbe drops below the level of acute infection. In clinical situations, the original cause will be completely invisible, and doctors will be reduced to treating symptoms.

Does this sound familiar?
 
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