The confused immune system, asthma, and EV-D68

School’s back in session and with it has come the unavoidable spread of infectious diseases.  Kids don’t always like to share their toys, but they can’t seem to help but bestowing upon their friends their nasty infections!  Gross!  It’s ok…I’m all about exposing kids to lots of germs….good practice for the immune system!  The infection to start out the 2014-2015 school year seems to be one called Enterovirus D68.  As of September 25, 2014, 220 people in 32 states have been confirmed to be infected with the virus.  That’s not such a huge number and it’s definitely not something that we should be flipping out about.

http://mashable.com/2013/06/18/panic-gifs/

Don’t panic!

Most people who are infected have symptoms of a common cold and recover after a few days of coughing, sneezing, and generally feeling blah. But it is causing hospitalizations especially among children who have a history of asthma.  Since there’s not a lot out there about the specific immune response to enterovirus, this week I thought I would discuss one of the reasons why those affected with asthma are oftentimes more prone to suffering complications due to viral infections.

There are a lot of reasons that people develop asthma, but about 50% of those afflicted are considered TH2 high.  Before we get into how this affects infections and asthma, we probably need to understand what TH2 means.  Helper T cells (one type of cell in the adaptive immune system) come in lots of flavors including TH1, TH2, TH17, TH22, TFH, TReg, yada yada yada.  It’s kind of ridiculous, and scientists are constantly adding to that list, probably just to make immunology as confusing as possible.  Or maybe the immune system is just that complicated! We’ll narrow down to TH1 and TH2 though.  TH1 cells “help” (thus the H) other cells to kill viruses and bacteria, usually the sort of nasty bugs that live inside of a cell. Think influenza, HIV, Tuberculosis, enterovirus D68.  TH2 cells on the other hand “help” other cells to kill parasites, worms, and some bacteria that live outside of cells.  (See picture below).  Getting rid of these two different types of pathogens (those that live inside the cell versus those that live outside of the cell) requires different weapons.  Kind of how a police force would use a different approach to a bad guy with hostages inside a house versus a bad guy running around on the streets.Slide1

A TH1 response is required to get rid of viruses, like the enterovirus that is causing so many hospitalizations.  In a lot of people with asthma, the immune system is a little confused and tends to respond to viruses (and other things like allergens) with the wrong “weapons”, using TH2 instead of TH1. One of the weapons that should be used during viral infection is the cytokine Interferon which tells cells go into antiviral mode.  Asthma patients seem to make less of this weapon and instead make use of other weapons that aren’t as useful for getting rid of a virus. (For more information about Interferon and Enterovirus D68 go to the nerd boost!)  Since the wrong (TH2) weapons are being used however, the virus is able to avoid the immune response and to survive much longer.

The use of TH2 also causes them to have asthma exacerbations.  One reason this might be the case is that the virus causes damage to the cells of the lung making it more permeable (or accessible) to allergens and other irritants.  In addition, lots of immune cells are brought to the lung, pummeling the tissue with all sorts of inflammatory stuff that cause the typical features of asthma to show up…wheezing, breathlessness, chest tightness, and coughing. Complications from these asthma flare ups leads to breathing difficulties and might make necessary a trip to the ER.

So to wrap up, Enterovirus D68 isn’t really a bug that the general population needs to be worried about.  But if you have asthma or know of someone who does, it would be wise to keep a close eye on symptoms if you’re feeling sick.  But otherwise, go out into the world, enjoy life, but wash your hands and cover your cough to protect your asthmatic friends!

 

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2 comments

  1. I think EV D68 pathogenesis is way more complicated than this. It makes sense that Enteroviruses would evolve ways to shunt cytokine profile from Th1 to Th2, and D68 may have done this. If you look at all the reported cases, there’s a lot of variability. There’s the well described respiratory failure in Asthmatics, but some D68 + non-asthmatics have zero respiratory symptoms and then die suddenly 2/2 myocardial or CNS involvement. Means the virus can easily disseminate in non-asthmatics and cause fatal disease in this population as well.

    If we assume EV D68 itself has evolved a way to bias immune cells toward Th2, it follows that this strain might trigger an “allergic” type response or asthma exac (in asthma/Th2 heavy patients) once some “threshold” level of Th2 biasing has been reached. In non-asthmatic, there is likely more “room” for Enterovirus induced Th2 biasing before you see allergic or asthma type symptoms, which may allow D68 to continue to evade antiviral immunity while the host remains asymptomatic. Then, presumably some trigger down the road leads back to TH1 biasing and subsequently causes massive tissue necrosis in EV D68 infected tissues 2/2 adaptive cell-mediated response…..Or maybe not. It does block TLR3 pathways, we know that.

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  2. Thanks for your comment Bradley! Yes I’m sure it’s much more complicated than what I’ve outlined here! The post kind of started with EV-D68 but evolved to describe why people with asthma have complications from respiratory viruses. That’s an interesting theory as to how the virus can get out of control in non-asthmatics through an initial evasion/skewing of the Th1/Th2 system. Not sure if you saw the “nerd boost” or not, but it does talk about how EV-D68 blocks the TLR3 pathway (https://omnimmune.wordpress.com/2014/09/25/ev-d68-nerd-boost/).

    You are of course very knowledgeable about the topic! Hope to see your feedback in the future!

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