Inflammasome-Independent Role for NLRP3 in Controlling Innate Antihelminth Immunity and Tissue Repair in the Lung
| Autor: | Paul R. Giacomin, Lindsay A. Dent, Avril A. B. Robertson, Ramon M. Eichenberger, Andreas Kupz, David Brough, Jesuthas Ajendra, Zainab Agha, Judith E. Allen, Alex Loukas, Martha M Cooper, Rafid Alhallaf, Alistair L Chenery, Brian H. K. Chan, Tara E. Sutherland, James E Parkinson |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
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Transcription
Genetic Inflammasomes Lung Diseases Parasitic Neutrophils animal diseases Mice 0302 clinical medicine Lectins Gene expression Eosinophilia Sulfones Nippostrongylus brasiliensis Lung Mice Knockout Sulfonamides 0303 health sciences biology integumentary system Effector Caspase 1 Inflammasome Mucosal Immunology beta-N-Acetylhexosaminidases 3. Good health Chemotaxis Leukocyte Indenes Nippostrongylus medicine.symptom medicine.drug chemical and pharmacologic phenomena Heterocyclic Compounds 4 or More Rings 03 medical and health sciences Immune system Immunity Macrophages Alveolar NLR Family Pyrin Domain-Containing 3 Protein medicine Animals Regeneration Furans Strongylida Infections 030304 developmental biology biochemical phenomena metabolism and nutrition biology.organism_classification Immunity Innate Neutrophilia Mice Inbred C57BL Immunology bacteria Interleukin-4 030215 immunology |
| Zdroj: | Chenery, A L, Alhallaf, R, Agha, Z, Ajendra, J, Parkinson, J E, Cooper, M M, Chan, B H K, Eichenberger, R M, Dent, L A, Robertson, A A B, Kupz, A, Brough, D, Loukas, A, Sutherland, T E, Allen, J E & Giacomin, P R 2019, ' Inflammasome-Independent Role for NLRP3 in Controlling Innate Antihelminth Immunity and Tissue Repair in the Lung ', Journal of Immunology, vol. 203, no. 10, pp. 2724-2734 . https://doi.org/10.4049/jimmunol.1900640, https://doi.org/10.4049/jimmunol.1900640 The Journal of Immunology Author Choice |
| Popis: | Key Points Nlrp3−/− mice have enhanced early antihelminth immunity in the lung. Type 2 immunity and repair responses are dysregulated in Nlrp3−/− mice. NLRP3 plays an inflammasome-independent role during Nippostrongylus infection. Alternatively activated macrophages are essential effector cells during type 2 immunity and tissue repair following helminth infections. We previously showed that Ym1, an alternative activation marker, can drive innate IL-1R–dependent neutrophil recruitment during infection with the lung-migrating nematode, Nippostrongylus brasiliensis, suggesting a potential role for the inflammasome in the IL-1–mediated innate response to infection. Although inflammasome proteins such as NLRP3 have important proinflammatory functions in macrophages, their role during type 2 responses and repair are less defined. We therefore infected Nlrp3−/− mice with N. brasiliensis. Unexpectedly, compared with wild-type (WT) mice, infected Nlrp3−/− mice had increased neutrophilia and eosinophilia, correlating with enhanced worm killing but at the expense of increased tissue damage and delayed lung repair. Transcriptional profiling showed that infected Nlrp3−/− mice exhibited elevated type 2 gene expression compared with WT mice. Notably, inflammasome activation was not evident early postinfection with N. brasiliensis, and in contrast to Nlrp3−/− mice, antihelminth responses were unaffected in caspase-1/11–deficient or WT mice treated with the NLRP3-specific inhibitor MCC950. Together these data suggest that NLRP3 has a role in constraining lung neutrophilia, helminth killing, and type 2 immune responses in an inflammasome-independent manner. |
| Databáze: | OpenAIRE |
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