|Chen, Fei -|
|Liu, Zhugong -|
|Rozo, Cristina -|
|Wu, Wenhui -|
|Bowdridge, Scot -|
|Wynn, Thomas -|
|Gauge, William -|
Submitted to: Nature Medicine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: October 15, 2011
Publication Date: January 15, 2012
Citation: Chen, F., Liu, Z., Rozo, C., Wu, W., Bowdridge, S., Wynn, T., Urban Jr, J.F., Gauge, W. 2012. An essential role for TH2-type response in limiting acute tissue damage during experimental helminth infection.. Nature Medicine. 18(2):260-6. Interpretive Summary: Helminth (worm) parasites can affect host lung tissue similar to allergens that induce hypersecretion of mucus, airway hyper- reactivity, and re-structuring of the tissues. These components of the host response to worms or allergens are essentially side effects of the mechanisms needed to eliminate parasites, but become annoying and sometimes unhealthy consequences of the response to allergens. Control of these side effects could be useful in limiting the expression of disease. The current study showed that there is an early phase when inflammatory cells and molecules are activated in the lung during the transient passage of worm parasites followed by a shift to anti-inflammatory processes that promote healing and tissue repair. A similar condition could be envisioned for removal of harmful allergens from the lung and restoration of normal function. The information is important to researchers who study the control of infectious diseases in humans and livestock, and the relationship between parasitic infection and allergic disease.
Technical Abstract: Helminths induce potent Th2-type immune responses that can lead to worm expulsion, but it remains undetermined whether components of this response can enhance the wound healing responses elicited as these large multi-cellular parasites traffic thru vital tissues. We used a model of helminth infection where intestinal nematode larvae migrate transiently through the lung causing considerable lung damage resulting in hemorrhaging and inflammation. Our findings showed that neutrophils recruited through early elevations in IL-17 contributed to lung damage while subsequent IL-4R signaling enhanced expression of tissue repair factors, including insulin-like growth factor 1, and anti-inflammatory factors, including IL-10, both of which independently controlled inflammation and hemorrhaging. These studies indicate an important role for the Th2-type immune response in mediating acute wound healing during helminth infection.