NLRC4 Inflammasome-Mediated Regulation of Eosinophilic Functions
1
조회
0
다운로드
1
인용
0
참고문헌
키워드
초록
Eosinophils play critical roles in the maintenance of homeostasis in innate and adaptive immunity. Although primarily known for their roles in parasitic infections and the development of Th2 cell responses, eosinophils also play complex roles in other immune responses ranging from anti-inflammation to defense against viral and bacterial infections. However, the contributions of pattern recognition receptors in general, and NOD-like receptors (NLRs) in particular, to eosinophil involvement in these immune responses remain relatively underappreciated. Our in vivo studies demonstrated that NLRC4 deficient mice had a decreased number of eosinophils and impaired Th2 responses after induction of an allergic airway disease model. Our in vitro data, utilizing human eosinophilic EoL-1 cells, suggested that TLR2 induction markedly induced pro-inflammatory responses and inflammasome forming NLRC4 and NLRP3. Moreover, activation by their specific ligands resulted in caspase-1 cleavage and mature IL-1β secretion. Interestingly, Th2 responses such as secretion of IL-5 and IL-13 decreased after transfection of EoL-1 cells with short interfering RNAs targeting human NLRC4. Specific induction of NLRC4 with PAM3CSK4 and flagellin upregulated the expression of IL-5 receptor and expression of Fc epsilon receptors (FcεR1α, FcεR2). Strikingly, activation of the NLRC4 inflammasome also promoted expression of the costimulatory receptor CD80 as well as expression of immunoregulatory receptors PD-L1 and Siglec-8. Concomitant with NLRC4 upregulation, we found an increase in expression and activation of matrix metalloproteinase (MMP)-9, but not MMP-2. Collectively, our results present new potential roles of NLRC4 in mediating a variety of eosinopilic functions.
Abstract
Eosinophils play critical roles in the maintenance of homeostasis in innate and adaptive immunity. Although primarily known for their roles in parasitic infections and the development of Th2 cell responses, eosinophils also play complex roles in other immune responses ranging from anti-inflammation to defense against viral and bacterial infections. However, the contributions of pattern recognition receptors in general, and NOD-like receptors (NLRs) in particular, to eosinophil involvement in these immune responses remain relatively underappreciated. Our in vivo studies demonstrated that NLRC4 deficient mice had a decreased number of eosinophils and impaired Th2 responses after induction of an allergic airway disease model. Our in vitro data, utilizing human eosinophilic EoL-1 cells, suggested that TLR2 induction markedly induced pro-inflammatory responses and inflammasome forming NLRC4 and NLRP3. Moreover, activation by their specific ligands resulted in caspase-1 cleavage and mature IL-1β secretion. Interestingly, Th2 responses such as secretion of IL-5 and IL-13 decreased after transfection of EoL-1 cells with short interfering RNAs targeting human NLRC4. Specific induction of NLRC4 with PAM3CSK4 and flagellin upregulated the expression of IL-5 receptor and expression of Fc epsilon receptors (FcεR1α, FcεR2). Strikingly, activation of the NLRC4 inflammasome also promoted expression of the costimulatory receptor CD80 as well as expression of immunoregulatory receptors PD-L1 and Siglec-8. Concomitant with NLRC4 upregulation, we found an increase in expression and activation of matrix metalloproteinase (MMP)-9, but not MMP-2. Collectively, our results present new potential roles of NLRC4 in mediating a variety of eosinopilic functions.
참고문헌 (62)
- Stone KD, "IgE, mast cells, basophils, and eosinophils", J Allergy Clin Immunol, 125, pp.S73~S80 (2010)
- Long H, "A player and coordinator : the versatile roles of eosinophils in the immune system", Transfus Med Hemother, 43, pp.96~108 (2016)
- McBrien CN, "The biology of eosinophils and their role in asthma", Front Med(Lausanne), 4, pp.93~ (2017)
- Ramirez GA, "Eosinophils from physiology to disease : a comprehensive review", BioMed Res Int, 2018, pp.9095275~ (2018)
- Weller PF, "Functions of tissue-resident eosinophils", Nat Rev Immunol, 17, pp.746~760 (2017)
- Fulkerson PC, "IL-5 triggers a cooperative cytokine network that promotes eosinophil precursor maturation", J Immunol, 193, pp.4043~4052 (2014)
- Esnault S, "Matrix metalloproteinase-9-dependent release of IL-1β by human eosinophils", Mediators Inflamm, 2019, pp.7479107~ (2019)
- Sugawara R, "Small intestinal eosinophils regulate Th17 cells by producing IL-1 receptor antagonist", J Exp Med, 213, pp.555~567 (2016)
- Drake MG, "Human and mouse eosinophils have antiviral activity against parainfluenza virus", Am J Respir Cell Mol Biol, 55, pp.387~394 (2016)
- Arnold IC, "Eosinophils suppress Th1 responses and restrict bacterially induced gastrointestinal inflammation", J Exp Med, 215, pp.2055~2072 (2018)
- Guerra ES, "Central role of IL-23 and IL-17 producing eosinophils as immunomodulatory effector cells in acute pulmonary aspergillosis and allergic asthma", PLoS Pathog, 13, pp.e1006175~ (2017)
- Ciraci C, "Control of innate and adaptive immunity by the inflammasome", Microbes Infect, 14, pp.1263~1270 (2012)
- Sharma D, "The cell biology of inflammasomes : Mechanisms of inflammasome activation and regulation", J Cell Biol, 213, pp.617~629 (2016)
- Duncan JA, "The NLRC4 inflammasome", Immunol Rev, 281, pp.115~123 (2018)
- Vance RE, "The NAIP", NLRC4 inflammasomes, 2015, pp.32, 84~89
- Broz P, "Differential requirement for caspase-1 autoproteolysis in pathogen-induced cell death and cytokine processing", Cell Host Microbe, 8, pp.471~483 (2010)
- Kvarnhammar AM, "Pattern-recognition receptors in human eosinophils", Immunology, 136, pp.11~20 (2012)
- Brattig NW, "The major surface protein of Wolbachia endosymbionts in filarial nematodes elicits immune responses through TLR2 and TLR4", J Immunol, 173, pp.437~445 (2004)
- Makepeace BL, "Granulocytes in helminth infection -- who is calling the shots?", Curr Med Chem, 19, pp.1567~1586 (2012)
- Lara-Tejero M, "Role of the caspase-1 inflammasome in Salmonella typhimurium pathogenesis", J Exp Med, 203, pp.1407~1412 (2006)
- Gram AM, "Salmonella flagellin activates NAIP", NLRC4 and canonical NLRP3 inflammasomes in human macrophages, 2021, pp.206, 631~640
- Lian L, "NLRC5 knockdown in chicken macrophages alters response to LPS and poly(I : C)stimulation", BMC Vet Res, 8, pp.23~ (2012)
- Ciraci C, "Avian-specific TLRs and downstream effector responses to CpG-induction in chicken macrophages", Dev Comp Immunol, 35, pp.392~398 (2011)
- Ozel I, "Adenosine-induced NLRP11 in B lymphoblasts suppresses human CD4+ T helper cell responses", J Immunol Res, 2020, pp.1421795~ (2020)
- 정윤재, "Comparative Analysis of Dibutyric cAMP and Butyric Acid on the Differentiation of Human Eosinophilic Leukemia EoL-1 Cells", Immune Network, 15(6), pp.313~318 (2015), 대한면역학회[DOI]
- Mayumi M, "EoL-1, a human eosinophilic cell line", Leuk Lymphoma, 7, pp.243~250 (1992)
- Kelley N, "The NLRP3 inflammasome : an overview of mechanisms of activation and regulation", Int J Mol Sci, 20, pp.3328~ (2019)
- He Y, "Mechanism and regulation of NLRP3 inflammasome activation", Trends Biochem Sci, 41, pp.1012~1021 (2016)
- Mehal WZ, "The inflammasome in liver injury and non-alcoholic fatty liver disease", Dig Dis, 32, pp.507~515 (2014)
- Reyes Ruiz VM, "Broad detection of bacterial type III secretion system and flagellin proteins by the human NAIP", NLRC4 inflammasome, 2017, pp.114, 13242~13247
- Zhao Y, "The NAIP-NLRC4 inflammasome in innate immune detection of bacterial flagellin and type III secretion apparatus", Immunol Rev, 265, pp.85~102 (2015)
- Molofsky AB, "Interleukin-33 in tissue homeostasis, injury, and inflammation", Immunity, 42, pp.1005~1019 (2015)
- Tahoun A, "Host species adaptation of TLR5 signalling and flagellin recognition", Sci Rep, 7, pp.17677~ (2017)
- Hassani M, "Immunological and hematological effects of IL-5(Rα)-targeted therapy : an overview", Allergy, 73, pp.1979~1988 (2018)
- Flores-Torres AS, "Eosinophils and respiratory viruses", Viral Immunol, 32, pp.198~207 (2019)
- Driss V, "TLR2-dependent eosinophil interactions with mycobacteria : role of α-defensins", Blood, 113, pp.3235~3244 (2009)
- Chu VT, "Eosinophils are required for the maintenance of plasma cells in the bone marrow", Nat Immunol, 12, pp.151~159 (2011)
- Nutku-Bilir E, "Interleukin-5 priming of human eosinophils alters siglec-8 mediated apoptosis pathways", Am J Respir Cell Mol Biol, 38, pp.121~124 (2008)
- Na HJ, "IL-33 enhances Siglec-8 mediated apoptosis of human eosinophils", Cytokine, 57, pp.169~174 (2012)
- Rodolpho JM, "Robust phenotypic activation of eosinophils during experimental Toxocara canis infection", Front Immunol, 9, pp.64~ (2018)
- Jiménez-Uribe AP, "CD80 expression correlates with IL-6 production in THP-1-like macrophages costimulated with LPS and dialyzable leukocyte extract(Transferon®)", J Immunol Res, 2019, pp.2198508~ (2019)
- Lim W, "Regulation of B7. 1 costimulatory molecule is mediated by the IFN regulatory factor-7 through the activation of JNK in lipopolysaccharide-stimulated human monocytic cells", J Immunol, 175, pp.5690~5700 (2005)
- Schwingshackl A, "Human eosinophils release matrix metalloproteinase-9 on stimulation with TNF-α", J Allergy Clin Immunol, 104, pp.983~989 (1999)
- Raffetto JD, "Matrix metalloproteinases and their inhibitors in vascular remodeling and vascular disease", Biochem Pharmacol, 75, pp.346~359 (2008)
- Cui N, "Biochemical and Biological Attributes of Matrix Metalloproteinases", Prog Mol Biol Transl Sci, 147, pp.1~73 (2017)
- Varricchi G, "Eosinophils : the unsung heroes in cancer", OncoImmunology, 7, pp.e1393134~ (2017)
- Vignola AM, "Sputum metalloproteinase-9", tissue inhibitor of metalloproteinase-1 ratio correlates with airflow obstruction in asthma and chronic bronchitis, 1998, pp.158, 1945~1950
- Dahlen B, "Immunohistochemical localisation of the matrix metalloproteinases MMP-3 and MMP-9 within the airways in asthma", Thorax, 54, pp.590~596 (1999)
- Vliagoftis H, "Proteinase-activated receptor-2-mediated matrix metalloproteinase-9 release from airway epithelial cells", J Allergy Clin Immunol, 106, pp.537~545 (2000)
- Brunner R, "The ABC of clinical and experimental adjuvants--a brief overview", Immunol Lett, 128, pp.29~35 (2010)
- Davoine F, "Eosinophil cytokines, chemokines, and growth factors : emerging roles in immunity", Front Immunol, 5, pp.570~ (2014)
- Pelaia C, "Interleukin-5 in the pathophysiology of severe asthma", Front Physiol, 10, pp.1514~ (2019)
- Kiwamoto T, "The role of lung epithelial ligands for Siglec-8 and Siglec-F in eosinophilic inflammation", Curr Opin Allergy Clin Immunol, 13, pp.106~111 (2013)
- Jia Y, "Expression of ligands for Siglec-8 and Siglec-9 in human airways and airway cells", J Allergy Clin Immunol, 135, pp.799~810.e7 (2015)
- Spencer LA, "Eosinophils and Th2 immunity : contemporary insights", Immunol Cell Biol, 88, pp.250~256 (2010)
- Fulkerson PC, "A central regulatory role for eosinophils and the eotaxin", CCR3 axis in chronic experimental allergic airway inflammation, 2006, pp.103, 16418~16423
- Walsh ER, "Strain-specific requirement for eosinophils in the recruitment of T cells to the lung during the development of allergic asthma", J Exp Med, 205, pp.1285~1292 (2008)
- Corry DB, "Decreased allergic lung inflammatory cell egression and increased susceptibility to asphyxiation in MMP2-deficiency", Nat Immunol, 3, pp.347~353 (2002)
- Gaidt MM, "Human monocytes engage an alternative inflammasome pathway", Immunity, 44, pp.833~846 (2016)
- Funderburg N, "Human-defensin-3 activates professional antigen-presenting cells via Toll-like receptors 1 and 2", Proc Natl Acad Sci U S A, 104, pp.18631~18635 (2007)
- Bochner BS, "Workshop report from the national institutes of health taskforce on the research needs of eosinophil-associated diseases (TREAD)", J Allergy Clin Immunol, 130, pp.587~596 (2012)
- Khoury P, "Revisiting the NIH Taskforce on the Research needs of Eosinophil-Associated Diseases(RE-TREAD)", J Leukoc Biol, 104, pp.69~83 (2018)