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Title: Macrophages as IL-25/IL-33-responsive cells play an important role in the induction of type 2 immunity

item YANG, ZHONGHAN - University Of Maryland
item GRINCHUK, VICTORIA - University Of Maryland
item Urban, Joseph
item BOHL, J - University Of Maryland
item SUN, REX - University Of Maryland
item NOTARI, LUIGI - University Of Maryland
item YAN, S - University Of Maryland
item RAMALINGAM, T - National Instiute Of Allergy And Infectious Diseases (NIAID, NIH)
item KEEGAN, A - University Of Maryland
item WYNN, T - National Instiute Of Allergy And Infectious Diseases (NIAID, NIH)
item SHEA-DONOHUE, T - University Of Maryland
item ZHAO, AIPING - University Of Maryland

Submitted to: PLOS ONE
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/30/2013
Publication Date: 2/25/2013
Citation: Yang, Z., Grinchuk, V., Urban Jr, J.F., Bohl, J., Sun, R., Notari, L., Yan, S., Ramalingam, T., Keegan, A.D., Wynn, T.A., Shea-Donohue, T., Zhao, A. 2013. Macrophages as IL-25/IL-33-responsive cells play an important role in the induction of type 2 immunity. PLoS One. 8(3):e59441,1-11.

Interpretive Summary: Helminth (worm) parasites can affect host allergic reactions and either enhance or reduce inflammation. The events that initiate recognition of the worm and induce an allergic response are not well known. The current study showed that common protein messenger molecules called IL-25 and IL-33 can activate the macrophage cell, which is often found in surfaces contacted by the worm, to release other proteins that contribute to allergy. An experimental model was developed that used a worm that infects mice called Heligmosomoides bakeri to show that transfer of these IL-25/IL-33 activated macrophages causes worm expulsion from the intestine. This work shows some of the early events that stimulate the host to respond to parasites and their products that include allergens. The information is important to researchers that study the control of infectious diseases in humans and livestock, and the relationship between parasitic infection and allergic disease.

Technical Abstract: Th2 immunity is essential for the host protection against nematode infection, while detrimental in allergic inflammation or asthma. Although many of the details regarding the cellular and molecular events in Th2 immunity have been described, the specific cell types and effector molecules involved in the initiation stage have not been entirely elucidated. In the development of Th2-dominant nematode infection, intestinal epithelia produce several cytokines, such as IL-25, IL-33, and TSLP, which are reported to play key roles in initiating host protective immunity. The identity of the cell types that mediate the IL-25/IL-33 effects on Th2 immunity is an area of intensive research, and recent studies suggest that several novel innate immune cell populations act as the IL-25/IL-33-responsive cells to produce Th2 cytokines. Macrophages are strategically located beneath the intestinal epithelium and previous studies indicated that macrophages are required for protective Th2 immunity against nematode infection. Here it was demonstrated that macrophages respond to IL-25/IL-33 to produce Th2 cytokines both in vitro and in vivo. Depleting macrophages with clodronate-containing liposomes in mice dramatically attenuated the IL-25/IL-33-induced Th2 immune responses and the characteristic changes in intestinal smooth muscle function. Furthermore, adoptive transfer of IL-25/IL-33-activated macrophages into mice with a chronic Heligmosomoides bakeri infection confers a protective response characterized by enhanced Th2 immunity. The current study reveals a previously unidentified role of macrophages as IL-25/IL-33-responsive cells in the induction of Th2 immunity.