The NLRP3 Inflammasome Suppresses Protective Immunity to Gastrointestinal Helminth Infection.
Cell Rep
; 23(4): 1085-1098, 2018 04 24.
Article
en En
| MEDLINE
| ID: mdl-29694887
ABSTRACT
Inflammasomes promote immunity to microbial pathogens by regulating the function of IL-1-family cytokines such as IL-18 and IL-1ß. 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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
3_ND
Problema de salud:
3_helminthiasis
/
3_neglected_diseases
/
3_zoonosis
Asunto principal:
Tricuriasis
/
Trichuris
/
Inmunidad Adaptativa
/
Proteína con Dominio Pirina 3 de la Familia NLR
/
Inmunidad Innata
/
Antígenos Helmínticos
Límite:
Animals
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Cell Rep
Año:
2018
Tipo del documento:
Article
País de afiliación:
Australia