IL-1β suppresses innate IL-25 and IL-33 production and maintains helminth chronicity.
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.
Global Health Institute, École Polytechnique Fédèrale de Lausanne, Switzerland.
Mario M
MM
Zaiss
Kendle M
KM
Maslowski
Ilaria
I
Mosconi
Nadine
N
Guenat
Benjamin J
BJ
Marsland
Nicola L
NL
Harris
D000818:Animals; D018501:Antirheumatic Agents / Q000494:pharmacology; D002908:Chronic Disease; D007113:Immunity, Innate; D018928:Immunity, Mucosal; D053590:Interleukin 1 Receptor Antagonist Protein / Q000494:pharmacology; D053583:Interleukin-1beta / Q000235:genetics / Q000276:immunology*; D000067596:Interleukin-33; D007378:Interleukins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009351:Nematospiroides dubius / Q000276:immunology*; D017206:Strongylida Infections / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology
D018501:Antirheumatic Agents; C506536:IL33 protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D053583:Interleukin-1beta; D000067596:Interleukin-33; D007378:Interleukins; C442281:Mydgf protein, mouse