IL-1β Suppresses Innate IL-25 and IL-33 Production and Maintains Helminth Chronicity

PLoS Pathogens

Kendle M. Maslowski¹  Benjamin J. Marsland²  Nadine Guenat³  Ilaria Mosconi³  Nicola L. Harris³  Mario M. Zaiss³ 

[1] Department of Biochemistry, University of Lausanne, Lausanne, Switzerland;Department of Pneumology, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland;Global Health Institute, École Polytechnique Fédèrale de Lausanne (EPFL), Lausanne, Switzerland

关键词: Gastrointestinal tract;    Cytokines;    Helminth infections;    Parasitic intestinal diseases;    Parasitic diseases;    Secretion;    Inflammasomes;    Helminths;   

DOI  :  10.1371/journal.ppat.1003531

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Approximately 2 billion people currently suffer from intestinal helminth infections, which are typically chronic in nature and result in growth retardation, vitamin A deficiency, anemia and poor cognitive function. Such chronicity results from co-evolution between helminths and their mammalian hosts; however, the molecular mechanisms by which these organisms avert immune rejection are not clear. We have found that the natural murine helminth, Heligmosomoides polygyrus bakeri (Hp) elicits the secretion of IL-1β in vivo and in vitro and that this cytokine is critical for shaping a mucosal environment suited to helminth chronicity. Indeed in mice deficient for IL-1β (IL-1β−/−), or treated with the soluble IL-1βR antagonist, Anakinra, helminth infection results in enhanced type 2 immunity and accelerated parasite expulsion. IL-1β acts to decrease production of IL-25 and IL-33 at early time points following infection and parasite rejection was determined to require IL-25. Taken together, these data indicate that Hp promotes the release of host-derived IL-1β that suppresses the release of innate cytokines, resulting in suboptimal type 2 immunity and allowing pathogen chronicity.

【 授权许可】

CC BY