Journal Article

Macrophages as IL-25/IL-33-Responsive Cells Play an Important Role in the Induction of Type 2 Immunity

Yang, Zhonghan, Wynn, Thomas A., Yan, Shu, Zhao, Aiping, Notari, Luigi, Shea-Donohue, Terez, Grinchuk, Viktoriya, Bohl, Jennifer, Ramalingam, Thirumalai, Keegan, Achsah D., Urban, Joseph F., Sun, Rex

2013

Overview

Type 2 immunity is essential for host protection against nematode infection but is detrimental in allergic inflammation or asthma. There is a major research focus on the effector molecules and specific cell types involved in the initiation of type 2 immunity. Recent work has implicated an important role of epithelial-derived cytokines, IL-25 and IL-33, acting on innate immune cells that are believed to be the initial sources of type 2 cytokines IL-4/IL-5/IL-13. The identities of the cell types that mediate the effects of IL-25/IL-33, however, remain to be fully elucidated. In the present study, we demonstrate that macrophages as IL-25/IL-33-responsive cells play an important role in inducing type 2 immunity using both in vitro and in vivo approaches. Macrophages produced type 2 cytokines IL-5 and IL-13 in response to the stimulation of IL-25/IL-33 in vitro, or were the IL-13-producing cells in mice administrated with exogenous IL-33 or infected with Heligmosomoides bakeri. In addition, IL-33 induced alternative activation of macrophages primarily through autocrine IL-13 activating the IL-4Rα-STAT6 pathway. Moreover, depletion of macrophages attenuated the IL-25/IL-33-induced type 2 immunity in mice, while adoptive transfer of IL-33-activated macrophages into mice with a chronic Heligmosomoides bakeri infection induced worm expulsion accompanied by a potent type 2 protective immune response. Thus, macrophages represent a unique population of the innate immune cells pivotal to type 2 immunity and a potential therapeutic target in controlling type 2 immunity-mediated inflammatory pathologies.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adoptive Transfer / Animals / Asthma / Autocrine signalling / Biology / Cell activation / Chronic infection / Cytokines / Cytokines - biosynthesis / Expulsion / Gastroenterology / Gene Expression Regulation - drug effects / Heligmosomoides bakeri / Hypersensitivity / Immune response / Immune system / Immunity / Immunology / Infections / Infectious diseases / Inflammation / Inflammatory diseases / Interleukin 13 / Interleukin 4 / Interleukin 5 / Interleukin-13 - biosynthesis / Interleukin-33 / Interleukins - administration & dosage / Interleukins - pharmacology / Laboratory animals / Macrophage Activation - drug effects / Macrophages / Macrophages - drug effects / Macrophages - immunology / Macrophages - metabolism / Medicine / Mice / Nematode Infections - immunology / Nematode Infections - prevention & control / Nematodes / Nutrition research / Parasitology / Rodents / Small intestine / Stat6 protein / Therapeutic applications / Viral infections