Endogenous innate sensor NLRP3 is a key component in peritoneal macrophage dynamics required for cestode establishment.

Autor: Flores-Sotelo I; Laboratorio de Inmunología Experimental y Regulación de la Inflamación Hepato-Intestinal, UBIMED, FES, Iztacala, UNAM, Tlalnepantla de Baz, Estado de México, Mexico., Juárez N; Laboratorio de Inmunología Experimental y Regulación de la Inflamación Hepato-Intestinal, UBIMED, FES, Iztacala, UNAM, Tlalnepantla de Baz, Estado de México, Mexico., González MI; Laboratorio de Inmunología Experimental y Regulación de la Inflamación Hepato-Intestinal, UBIMED, FES, Iztacala, UNAM, Tlalnepantla de Baz, Estado de México, Mexico., Chávez A; Laboratorio de Inmunología Experimental y Regulación de la Inflamación Hepato-Intestinal, UBIMED, FES, Iztacala, UNAM, Tlalnepantla de Baz, Estado de México, Mexico., Vannan DT; Boston Scientific Corporation, Urology Division, 200 Boston Scientific Way, Marlborough, MA, USA., Eksteen B; Aspen Woods Clinic, Calgary, AB, Canada., Terrazas LI; Laboratorio de Inmunoparasitología, UBIMED, FES Iztacala, UNAM, Tlalnepantla de Baz, Estado de México, Mexico., Reyes JL; Laboratorio de Inmunología Experimental y Regulación de la Inflamación Hepato-Intestinal, UBIMED, FES, Iztacala, UNAM, Tlalnepantla de Baz, Estado de México, Mexico. jlreyes@iztacala.unam.mx.
Jazyk: angličtina
Zdroj: Immunologic research [Immunol Res] 2024 Oct; Vol. 72 (5), pp. 948-963. Date of Electronic Publication: 2024 Jun 06.
DOI: 10.1007/s12026-024-09496-3
Abstrakt: The NLRP3 receptor can assemble inflammasome platforms to trigger inflammatory responses; however, accumulating evidence suggests that it can also display anti-inflammatory properties. Here, we explored the role of nucleotide-binding oligomerization domain pyrin-containing protein 3 (NLRP3) in Taenia crassiceps experimental infection, which requires immune polarization into a Th2-type profile and peritoneal influx of suppressive macrophages for successful colonization. NLRP3 deficient mice (NLRP3 -/- ) were highly resistant against T. crassiceps, relative to wild-type (WT) mice. Resistance in NLRP3 -/- mice was associated with a diminished IL-4 output, high levels of IL-15, growth factor for both innate and adaptive lymphocytes, and a dramatic decrease in peritoneum-infiltrating suppressive macrophages. Also, a transcriptional analysis on bone marrow-derived macrophages exposed to Taenia-secreted antigens and IL-4 revealed that NLRP3 -/- macrophages express reduced transcripts of relm-α and PD-1 ligands, markers of alternative activation and suppressive ability, respectively. Finally, we found that the resistance displayed by NLRP3 -/- mice is transferred through intestinal microbiota exchange, since WT mice co-housed with NLRP3 -/- mice were significantly more resistant than WT animals preserving their native microbiota. Altogether, these data demonstrate that NLRP3 is a component of innate immunity required for T. crassiceps to establish, most likely contributing to macrophage recruitment, and controlling lymphocyte-stimulating cytokines such as IL-15.
Competing Interests: Declarations Conflicts of interest The authors declare no competing interests. Institutional review board statement The study was approved by the FES-Iztacala Bioethics Committee (CE/FESI/042022/1513) and met the recommended guidelines issued by government for experimental animal care (NOM-062-ZOO-1999). Informed consent Not applicable.
(© 2024. The Author(s).)
Databáze: MEDLINE
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