ASC and NLRP3 maintain innate immune homeostasis in the airway through an inflammasome-independent mechanism
| Autor: | Ikuo Kawamura, Kohsuke Tsuchiya, Shunsuke Sakai, Ryosuke Uchiyama, Hideki Hara, Masao Mitsuyama, Takashi Suda, Rendong Fang, Hiroko Tsutsui |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Inflammasomes Neutrophils Immunology Regulator Respiratory Mucosa Pneumococcal Infections 03 medical and health sciences Mice 0302 clinical medicine Immunity Genes Reporter NLR Family Pyrin Domain-Containing 3 Protein medicine Immunology and Allergy Animals Homeostasis Transcription factor Immunity Mucosal Caspase STAT6 Mice Knockout Innate immune system integumentary system biology Proto-Oncogene Proteins c-ets Caspase 1 Inflammasome medicine.disease Flow Cytometry Caspases Initiator Immunity Innate CARD Signaling Adaptor Proteins 030104 developmental biology Streptococcus pneumoniae Neutrophil Infiltration Pneumococcal pneumonia biology.protein Cytokines STAT6 Transcription Factor 030215 immunology medicine.drug |
| Zdroj: | Mucosal immunology. 12(5) |
| ISSN: | 1935-3456 |
| Popis: | It is widely accepted that inflammasomes protect the host from microbial pathogens by inducing inflammatory responses through caspase-1 activation. Here, we show that the inflammasome components ASC and NLRP3 are required for resistance to pneumococcal pneumonia, whereas caspase-1 and caspase-11 are dispensable. In the lung of S. pneumoniae-infected mice, ASC and NLRP3, but not caspase-1/11, were required for optimal expression of several mucosal innate immune proteins. Among them, TFF2 and intelectin-1 appeared to be protective against pneumococcal pneumonia. During infection, ASC and NLRP3 maintained the expression of the transcription factor SPDEF, which can facilitate the expression of the mucosal defense factor genes. Moreover, activation of STAT6, a key regulator of Spdef expression, depended on ASC and NLRP3. Overexpression of these inflammasome proteins sustained STAT6 phosphorylation induced by type 2 cytokines. Collectively, this study suggests that ASC and NLRP3 promote airway mucosal innate immunity by an inflammasome-independent mechanism involving the STAT6-SPDEF pathway. |
| Databáze: | OpenAIRE |
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