43. Reiniger N, Lee MM, Coleman FT, Ray C, Golan DE, et al. (2007) Resistance to Pseudomonas aeruginosa Chronic Lung Infection Requires Cystic Fibrosis Transmembrane Conductance Regulator-Modulated Interleukin-1 (IL-1) Re- lease and Signaling through the IL-1 Receptor. Infect Immun 75: 1598–1608. 44. Gasse P, Mary C, Guenon I, Noulin N, Charron S, et al. (2007) IL-1R1/MyD88 signaling and the inflammasome are essential in pulmonary inflammation and fibrosis in mice. The Journal of Clinical Investigation 117: 3786–3799. 45. Churg A, Zhou S, Wang X, Wang R, Wright JL (2009) The role of interleukin- 1beta in murine cigarette smoke-induced emphysema and small airway remodeling. Am J Respir Cell Mol Biol 40: 482–490. 46. Blohmke CJ, Victor RE, Hirschfeld AF, Elias IM, Hancock DG, et al. (2008) Innate immunity mediated by TLR5 as a novel antiinflammatory target for cystic fibrosis lung disease. J Immunol 180: 7764–7773. 47. Ward JR, West PW, Ariaans MP, Parker LC, Francis SE, et al. (2010) Temporal interleukin-1beta secretion from primary human peripheral blood monocytes by P2X7-independent and P2X7-dependent mechanisms. J Biol Chem 285: 23147–23158. 48. Netea MG, Nold-Petry CA, Nold MF, Joosten LA, Opitz B, et al. (2009) Differential requirement for the activation of the inflammasome for processing and release of IL-1beta in monocytes and macrophages. Blood 113: 2324–2335. 49. Piccini A, Carta S, Tassi S, Lasiglie´ D, Fossati G, et al. (2008) ATP is released by monocytes stimulated with pathogen-sensing receptor ligands and induces IL-1b and IL-18 secretion in an autocrine way. Proceedings of the National Academy of Sciences 105: 8067–8072. 50. Del Porto P, Cifani N, Guarnieri S, Di Domenico EG, Mariggio MA, et al. (2011) Dysfunctional CFTR alters the bactericidal activity of human macrophages against Pseudomonas aeruginosa. PLoS ONE 6: e19970. 51. Sorio C, Buffelli M, Angiari C, Ettorre M, Johansson J, et al. (2011) Defective CFTR expression and function are detectable in blood monocytes: development of a new blood test for cystic fibrosis. PLoS ONE 6: e22212. 52. Konstan MW, Hilliard KA, Norvell TM, Berger M (1994) Bronchoalveolar lavage findings in cystic fibrosis patients with stable, clinically mild lung disease suggest ongoing infection and inflammation. Am J Respir Crit Care Med 150: 448–454. IL-1b Production in Cystic Fibrosis 53. Hilliard TN, Regamey N, Shute JK, Nicholson AG, Alton EW, et al. (2007) Airway remodelling in children with cystic fibrosis. Thorax 62: 1074–1080. 54. Khan TZ, Wagener JS, Bost T, Martinez J, Accurso FJ, et al. (1995) Early pulmonary inflammation in infants with cystic fibrosis. Am J Respir Crit Care Med 151: 1075–1082. 55. van de Veerdonk FL, Netea MG, Dinarello CA, Joosten LA. Inflammasome activation and IL-1beta and IL-18 processing during infection. Trends Immunol 32: 110–116. 56. Greten FR, Arkan MC, Bollrath J, Hsu L-C, Goode J, et al. (2007) NF-kB Is a Negative Regulator of IL-1b Secretion as Revealed by Genetic and Pharmacological Inhibition of IKKb. Cell 130: 918–931. 57. Zheng Y, Lilo S, Brodsky IE, Zhang Y, Medzhitov R, et al. (2011) A Yersinia effector with enhanced inhibitory activity on the NF-kappaB pathway activates the NLRP3/ASC/caspase-1 inflammasome in macrophages. PLoS Pathog 7: e1002026. 58. Kunsch C, Rosen CA (1993) NF-kappa B subunit-specific regulation of the interleukin-8 promoter. Mol Cell Biol 13: 6137–6146. 59. Sander LE, Davis MJ, Boekschoten MV, Amsen D, Dascher CC, et al. (2011) Detection of prokaryotic mRNA signifies microbial viability and promotes immunity. Nature 474: 385–389. 60. Smith EE, Buckley DG, Wu Z, Saenphimmachak C, Hoffman LR, et al. (2006) Genetic adaptation by Pseudomonas aeruginosa to the airways of cystic fibrosis patients. Proc Natl Acad Sci U S A 103: 8487–8492. 61. Roy-Burman A, Savel RH, Racine S, Swanson BL, Revadigar NS, et al. (2001) Type III Protein Secretion Is Associated with Death in Lower Respiratory and Systemic Pseudomonas aeruginosa Infections. Journal of Infectious Diseases 183: 1767–1774. 62. Blohmke CJ, Park J, Hirschfeld AF, Victor RE, Schneiderman J, et al. (2010) TLR5 as an Anti-Inflammatory Target and Modifier Gene in Cystic Fibrosis. The Journal of Immunology 185: 7731–7738. 63. Hirschfeld AF, Bettinger JA, Victor RE, Davidson DJ, Currie AJ, et al. (2007) Prevalence of Toll-like receptor signalling defects in apparently healthy children who developed invasive pneumococcal infection. Clin Immunol 122: 271–278. PLoS ONE | www.plosone.org 12 May 2012 | Volume 7 | Issue 5 | e37689