Production of IL-1β and Inflammasome with Up-Regulated Expressions of NOD-Like Receptor Related Genes in Toxoplasma gondii-Infected THP-1 Macrophages
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Toxoplasma gondii is an obligate intracellular parasite that stimulates production of high levels of proinflammatory cytokines, which are important for innate immunity. NLRs, i.e., nucleotide-binding oligomerization domain (NOD)-like receptors, play a crucial role as innate immune sensors and form multiprotein complexes called inflammasomes, which mediate caspase-1-dependent processing of pro-IL-1β. To elucidate the role of inflammasome components in T. gondii-infected THP-1 macrophages, we examined inflammasome-related gene expression and mechanisms of inflammasome-regulated cytokine IL-1β secretion. The results revealed a significant upregulation of IL-1β after T. gondii infection. T. gondii infection also upregulated the expression of inflammasome sensors, including NLRP1, NLRP3, NLRC4, NLRP6, NLRP8, NLRP13, AIM2, and NAIP, in a time-dependent manner. The infection also upregulated inflammasome adaptor protein ASC and caspase-1 mRNA levels. From this study, we newly found that T. gondii infection regulates NLRC4, NLRP6, NLRP8, NLRP13, AIM2, and neuronal apoptosis inhibitor protein (NAIP) gene expressions in THP-1 macrophages and that the role of the inflammasome-related genes may be critical for mediating the innate immune responses to T. gondii infection.
Abstract
Toxoplasma gondii is an obligate intracellular parasite that stimulates production of high levels of proinflammatory cytokines, which are important for innate immunity. NLRs, i.e., nucleotide-binding oligomerization domain (NOD)-like receptors, play a crucial role as innate immune sensors and form multiprotein complexes called inflammasomes, which mediate caspase-1-dependent processing of pro-IL-1β. To elucidate the role of inflammasome components in T. gondii-infected THP-1 macrophages, we examined inflammasome-related gene expression and mechanisms of inflammasome-regulated cytokine IL-1β secretion. The results revealed a significant upregulation of IL-1β after T. gondii infection. T. gondii infection also upregulated the expression of inflammasome sensors, including NLRP1, NLRP3, NLRC4, NLRP6, NLRP8, NLRP13, AIM2, and NAIP, in a time-dependent manner. The infection also upregulated inflammasome adaptor protein ASC and caspase-1 mRNA levels. From this study, we newly found that T. gondii infection regulates NLRC4, NLRP6, NLRP8, NLRP13, AIM2, and neuronal apoptosis inhibitor protein (NAIP) gene expressions in THP-1 macrophages and that the role of the inflammasome-related genes may be critical for mediating the innate immune responses to T. gondii infection.
참고문헌 (28)
- Flegr J, "Toxoplasmosis-a global threat. Correlation of latent toxoplasmosis with specific disease burden in a set of 88 countries", PLoS One, 9, pp.e90203~ (2014)
- Montoya JG, "Toxoplasmosis", Lancet, 363, pp.1965~1976 (2004)
- Yarovinsky F, "Innate immunity to Toxoplasma gondii infection", Nat Rev Immunol, 14, pp.109~121 (2014)
- Kawai T, "Innate immune recognition of viral infection", Nat Immunol, 7, pp.131~137 (2006)
- Meylan E, "Intracellular pattern recognition receptors in the host response", Nature, 442, pp.39~44 (2006)
- Olive C, "Pattern recognition receptors: sentinels in innate immunity and targets of new vaccine adjuvants", Expert Rev Vaccines, 11, pp.237~256 (2012)
- Kumar H, "Pathogen recognition by the innate immune system", Int Rev Immunol, 30, pp.16~34 (2011)
- Yarovinsky F, "Toll-like receptors and their role in host resistance to Toxoplasma gondii", Immunol Lett, 119, pp.17~21 (2008)
- Franchi L, "Function of Nod-like receptors in microbial recognition and host defense", Immunol Rev, 227, pp.106~128 (2009)
- Shaw MH, "NOD-like receptors(NLRs) : bona fide intracellular microbial sensors", Curr Opin Immunol, 20, pp.377~382 (2008)
- Lamkanfi M, "Mechanisms and functions of inflammasomes", Cell, 157, pp.1013~1022 (2014)
- Davis BK, "The inflammasome NLRs in immunity, inflammation, and associated diseases", Ann Rev Immunol, 29, pp.707~735 (2011)
- Witola WH, "NALP1 influences susceptibility to human congenital toxoplasmosis, proinflammatory cytokine response, and fate of Toxoplasma gondii-infected monocytic cells", Infect Immun, 79, pp.756~766 (2011)
- Wang S, "Toxoplasma gondii mitogen-activated protein kinases are associated with inflammasome activation in infected mice", Microbes Infect, 18, pp.696~700 (2016)
- Cirelli KM, "Inflammasome sensor NLRP1 controls rat macrophage susceptibility to Toxoplasma gondii", PLoS Pathog, 10, pp.e1003927~ (2014)
- Gorfu G, "Dual role for inflammasome sensors NLRP1 and NLRP3 in murine resistance to Toxoplasma gondii", MBio, 5, pp.e01117-13~ (2014)
- Ewald SE, "NLRP1 is an inflammasome sensor for Toxoplasma gondii", Infect Immun, 82, pp.460~468 (2014)
- Witola WH, "NALP1 influences susceptibility to human congenital toxoplasmosis, proinflammatory cytokine response, and fate of Toxoplasma gondii-infected monocytic cells", Infect Immun, 79, pp.756~766 (2011)
- Satoh T, "The inflammasome and IL-1β: implications for the treatment of inflammatory diseases", Immunotherapy, 7, pp.243~254 (2015)
- Dinarello CA, "A clinical perspective of IL-1beta as the gatekeeper of inflammation", Eur J Immunol, 41, pp.1203~1217 (2011)
- van de Veerdonk FL, "Inflammasome activation and IL-1β and IL-18 processing during infection", Trends Immunol, 32, pp.110~116 (2011)
- Marshall ES, "Toxoplasma gondii peroxiredoxin promotes altered macrophage function, caspase-1-dependent IL-1β secretion enhances parasite replication", Vet Res, 42, pp.80~ (2011)
- Nagineni CN, "Toxoplasma gondii infection induces gene expression and secretion of interleukin 1 (IL-1), IL-6, granulocyte-macrophage colony-stimulating factor, and intercellular adhesion molecule 1 by human retinal pigment epithelial cells", Infect Immun, 68, pp.407~410 (2000)
- Quan JH, "Involvement of PI 3 kinase", Akt-dependent Bad phosphorylation in Toxoplasma gondii-mediated inhibition of host cell apoptosis, 2013, pp.133, 462~471
- Sellin ME, "Inflammasomes of the intestinal epithelium", Trends Immunol, 36, pp.442~450 (2015)
- Moon H. Nahm, "NOD-Like Receptors in Infection, Immunity, and Diseases", Yonsei Medical Journal, 57(1), pp.5~14 (2016), 연세대학교의과대학[DOI]
- Lage SL, "Emerging concepts about NAIP", NLRC4 inflammasomes, 2014, pp.5, 309~
- Gov L, "Human innate immunity to Toxoplasma gondii is mediated by host caspase-1 and ASC and parasite GRA15", MBio, 4, pp.e00255-13~ (2013)