The NLRP3 Inflammasome Suppresses Protective Immunity to Gastrointestinal Helminth Infection

Alhallaf, R; Agha, Z; Miller, CM; Robertson, AAB; Sotillo, J; Croese, J; Cooper, MA; Masters, SL; Kupz, A; Smith, NC; Loukas, A; Giacomin, PR

The NLRP3 Inflammasome Suppresses Protective Immunity to Gastrointestinal Helminth Infection

Alhallaf, R Agha, Z Miller, CM Robertson, AAB Sotillo, J Croese, J Cooper, MA Masters, SL Kupz, A Smith, NC

Loukas, A Giacomin, PR

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Publication Type:: Journal Article
Citation:: Cell Reports, 2018, 23 (4), pp. 1085 - 1098
Issue Date:: 2018-04-24

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Field	Value	Language
dc.contributor.author	Alhallaf, R	en_US
dc.contributor.author	Agha, Z	en_US
dc.contributor.author	Miller, CM	en_US
dc.contributor.author	Robertson, AAB	en_US
dc.contributor.author	Sotillo, J	en_US
dc.contributor.author	Croese, J	en_US
dc.contributor.author	Cooper, MA	en_US
dc.contributor.author	Masters, SL	en_US
dc.contributor.author	Kupz, A	en_US
dc.contributor.author	Smith, NC https://orcid.org/0000-0002-7467-1451	en_US
dc.contributor.author	Loukas, A	en_US
dc.contributor.author	Giacomin, PR	en_US
dc.date.available	2018-03-21	en_US
dc.date.issued	2018-04-24	en_US
dc.identifier.citation	Cell Reports, 2018, 23 (4), pp. 1085 - 1098	en_US
dc.identifier.uri	http://hdl.handle.net/10453/131079
dc.description.abstract	© 2018 The Author(s) Inflammasomes promote immunity to microbial pathogens by regulating the function of IL-1-family cytokines such as IL-18 and IL-1β. However, the roles for inflammasomes during parasitic helminth infections remain unclear. We demonstrate that mice and humans infected with gastrointestinal nematodes display increased IL-18 secretion, which in Trichuris-infected or worm antigen-treated mice and in macrophages co-cultured with Trichuris antigens or exosome-like vesicles was dependent on the NLRP3 inflammasome. NLRP3-deficient mice displayed reduced pro-inflammatory type 1 cytokine responses and augmented protective type 2 immunity, which was reversed by IL-18 administration. NLRP3-dependent suppression of immunity partially required CD4+ cells but was apparent even in Rag1−/− mice that lack adaptive immune cells, suggesting that NLRP3 influences both innate and adaptive immunity. These data highlight a role for NLRP3 in limiting protective immunity to helminths, suggesting that targeting the NLRP3 inflammasome may be an approach for limiting the disease burden associated with helminth infections. Inflammasomes can protect us against infections with bacteria and viruses, but Alhallaf et al. now find that these inflammasomes may also actually prevent our immune system from being able to fight parasitic worm infections.	en_US
dc.relation.ispartof	Cell Reports	en_US
dc.relation.isbasedon	10.1016/j.celrep.2018.03.097	en_US
dc.subject.mesh	Th1 Cells	en_US
dc.subject.mesh	Th2 Cells	en_US
dc.subject.mesh	Animals	en_US
dc.subject.mesh	Mice, Knockout	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Mice	en_US
dc.subject.mesh	Trichuris	en_US
dc.subject.mesh	Trichuriasis	en_US
dc.subject.mesh	Antigens, Helminth	en_US
dc.subject.mesh	Cytokines	en_US
dc.subject.mesh	Female	en_US
dc.subject.mesh	Male	en_US
dc.subject.mesh	Immunity, Innate	en_US
dc.subject.mesh	Adaptive Immunity	en_US
dc.subject.mesh	NLR Family, Pyrin Domain-Containing 3 Protein	en_US
dc.title	The NLRP3 Inflammasome Suppresses Protective Immunity to Gastrointestinal Helminth Infection	en_US
dc.type	Journal Article
utslib.citation.volume	4	en_US
utslib.citation.volume	23	en_US
utslib.for	0601 Biochemistry and Cell Biology	en_US
utslib.for	1116 Medical Physiology	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
utslib.copyright.status	open_access
pubs.issue	4	en_US
pubs.publication-status	Published	en_US
pubs.volume	23	en_US

Abstract:

© 2018 The Author(s) Inflammasomes promote immunity to microbial pathogens by regulating the function of IL-1-family cytokines such as IL-18 and IL-1β. However, the roles for inflammasomes during parasitic helminth infections remain unclear. We demonstrate that mice and humans infected with gastrointestinal nematodes display increased IL-18 secretion, which in Trichuris-infected or worm antigen-treated mice and in macrophages co-cultured with Trichuris antigens or exosome-like vesicles was dependent on the NLRP3 inflammasome. NLRP3-deficient mice displayed reduced pro-inflammatory type 1 cytokine responses and augmented protective type 2 immunity, which was reversed by IL-18 administration. NLRP3-dependent suppression of immunity partially required CD4+ cells but was apparent even in Rag1−/− mice that lack adaptive immune cells, suggesting that NLRP3 influences both innate and adaptive immunity. These data highlight a role for NLRP3 in limiting protective immunity to helminths, suggesting that targeting the NLRP3 inflammasome may be an approach for limiting the disease burden associated with helminth infections. Inflammasomes can protect us against infections with bacteria and viruses, but Alhallaf et al. now find that these inflammasomes may also actually prevent our immune system from being able to fight parasitic worm infections.

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http://hdl.handle.net/10453/131079