Critical Role for Interleukin-25 in Host Protective Th2 Memory Response against Heligmosomoides polygyrus bakeri.
Infection with parasitic nematodes, especially gastrointestinal geohelminths, affects hundreds of millions of people worldwide and thus poses a major risk to global health. The host mechanism of defense against enteric nematode infection remains to be fully understood, but it involves a polarized type 2 immunity leading to alterations in intestinal function that facilitate worm expulsion. We investigated the role of interleukin-25 (IL-25) in host protection against Heligmosomoides polygyrus bakeri infection in mice. Our results showed that Il25 and its receptor subunit, Il17rb, were upregulated during a primary infection and a secondary challenge infection with H. polygyrus bakeri Genetic deletion of IL-25 (IL-25-/-) led to an attenuated type 2 cytokine response and increased worm fecundity in mice with a primary H. polygyrus bakeri infection. In addition, the full spectrum of the host memory response against a secondary infection with H. polygyrus bakeri was severely impaired in IL-25-/-mice, including delayed type 2 cytokine responses, an attenuated functional response of the intestinal smooth muscle and epithelium, diminished intestinal smooth muscle hypertrophy/hyperplasia, and impaired worm expulsion. Furthermore, exogenous administration of IL-25 restored the host protective memory response against H. polygyrus bakeri infection in IL-25-/-mice. These data demonstrate that IL-25 is critical for host protective immunity against H. polygyrus bakeri infection, highlighting its potential application as a therapeutic agent against parasitic nematode infection worldwide.
Department of Radiation Oncology and Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA.|Department of Gynecology and Obstetrics, XiangYa Hospital of Central South University, ChangSha, China.
Chenlin
C
Pei
Department of Radiation Oncology and Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Chao
C
Zhao
Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Nanchang University, Nanchang, China.
An-Jiang
AJ
Wang
Department of Radiation Oncology and Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Anya X
AX
Fan
Department of Radiation Oncology and Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Viktoriya
V
Grinchuk
U.S. Department of Agriculture, Agricultural Research Service, Beltsville Human Nutrition Research Center, Diet, Genomics, and Immunology Laboratory, Beltsville, Maryland, USA.
Allen
A
Smith
Department of Radiation Oncology and Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Rex
R
Sun
U.S. Department of Agriculture, Agricultural Research Service, Beltsville Human Nutrition Research Center, Diet, Genomics, and Immunology Laboratory, Beltsville, Maryland, USA.|Department of Parasitology, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China.
Yue
Y
Xie
Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Nanchang University, Nanchang, China.
Nonghua
N
Lu
U.S. Department of Agriculture, Agricultural Research Service, Beltsville Human Nutrition Research Center, Diet, Genomics, and Immunology Laboratory, Beltsville, Maryland, USA.
Joseph F
JF
Urban
Department of Radiation Oncology and Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Terez
T
Shea-Donohue
Department of Radiation Oncology and Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA aiping.zhao@nih.gov yangzhh@mail.sysu.edu.cn.
Aiping
A
Zhao
Department of Biochemistry, Zhongshan Medical School, Sun Yat-sen University, Guangzhou, China aiping.zhao@nih.gov yangzhh@mail.sysu.edu.cn.
Zhonghan
Z
Yang
D000818:Animals; D001119:Arginase / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000276:immunology; D006729:Hormones, Ectopic / Q000235:genetics / Q000378:metabolism; D007156:Immunologic Memory / Q000502:physiology*; D036341:Intercellular Signaling Peptides and Proteins; D007378:Interleukins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009351:Nematospiroides dubius / Q000276:immunology*; D053722:Receptors, Interleukin-17 / Q000235:genetics / Q000378:metabolism; D017206:Strongylida Infections / Q000276:immunology / Q000662:veterinary*; D018418:Th2 Cells / Q000502:physiology*; D015854:Up-Regulation
D006729:Hormones, Ectopic; C485810:Il17rb protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D007378:Interleukins; C442281:Mydgf protein, mouse; D053722:Receptors, Interleukin-17; C486522:Retnlb protein, mouse; C544448:Arg1 protein, mouse; D001119:Arginase