Natural killer (NK) cells are multicompetent lymphocytes of the innate immune system that play a central role in host defense and immune regulation. Although increasing evidence suggests that innate immunity plays a key role in the pathogenesis of chronic rhinosinusitis (CRS), the role of NK cells in CRS has been poorly studied. This study aimed to characterize the peripheral blood NK cells from patients with CRS, and to compare the functions of these cells with those from non-CRS controls. The correlation between NK cell functional activity and prognosis was also assessed. Eighteen CRS patients and 19 healthy non-CRS controls were included. The patients with CRS were classified into two subgroups, namely a treatment-responsive group and recalcitrant group. NK cell degranulation was determined by measuring the cell surface expression of CD107a against 721.221 and K562 cells. Intracytoplasmic cytokine production was determined by flow cytometry. Compared to the controls, the NK cells of CRS group had an impaired ability to degranulate and to produce cytokines such as IFN-γ and TNF-α. The recalcitrant subgroup showed the most severe defects in NK cell effector functions. Moreover, the decreased NK cell functions in patients with CRS were associated with poor prognostic factors such as concomitant asthma and peripheral blood eosinophilia. NK cells, which were originally named for their ability to mediate spontaneous cytotoxicity towards diseased cells including infected cells, may play an important role in regulating the inflammatory process in CRS pathogenesis.
References
[1]
Rosenfeld RM, Andes D, Bhattacharyya N, Cheung D, Eisenberg S, et al. (2007) Clinical practice guideline: adult sinusitis. Otolaryngol Head Neck Surg 137: S1–S31.
[2]
Hamilos DL (2011) Chronic rhinosinusitis: Epidemiology and medical management. J Allergy Clin Immunol 128: 693–707.
[3]
Lee S, Lane AP (2011) Chronic rhinosinusitis as a multifactorial inflammatory disorder. Curr Infect Dis Rep 13: 159–168.
[4]
Lane AP (2009) The role of innate immunity in the pathogenesis of chronic rhinosinusitis. Curr Allergy Asthma Rep 9: 205–212.
[5]
Cao PP, Li HB, Wang BF, Wang SB, You XJ, et al. (2009) Distinct immunopathologic characteristics of various types of chronic rhinosinusitis in adult Chinese. J Allergy Clin Immunol 124: 478–484.
Ramanathan M Jr, Lane AP (2007) Innate immunity of the sinonasal cavity and its role in chronic rhinosinusitis. Otolaryngol Head Neck Surg 136: 348–356.
[8]
Vivier E, Tomasello E, Baratin M, Walzer T, Ugolini S (2008) Functions of natural killer cells. Nat Immunol 9: 503–510.
[9]
Wesselkamper SC, Eppert BL, Motz GT, Lau GW, Hassett DJ, et al. (2008) NKG2D is critical for NK cell activation in host defense against Pseudomonas aeruginosa respiratory infection. J Immunol 181: 5481–5489.
[10]
Schierloh P, Aleman M, Yokobori N, Alves L, Roldan N, et al. (2005) NK cell activity in tuberculosis is associated with impaired CD11a and ICAM-1 expression: a regulatory role of monocytes in NK activation. Immunology 116: 541–552.
[11]
Vankayalapati R, Wizel B, Weis SE, Safi H, Lakey DL, et al. (2002) The NKp46 receptor contributes to NK cell lysis of mononuclear phagocytes infected with an intracellular bacterium. J Immunol 168: 3451–3457.
[12]
Prieto A, Reyes E, Bernstein ED, Martinez B, Monserrat J, et al. (2001) Defective natural killer and phagocytic activities in chronic obstructive pulmonary disease are restored by glycophosphopeptical (inmunoferon). Am J Respir Crit Care Med 163: 1578–1583.
[13]
Fairclough L, Urbanowicz RA, Corne J, Lamb JR (2008) Killer cells in chronic obstructive pulmonary disease. Clin Sci 114: 533–541.
[14]
Wei H, Zhang J, Xiao W, Feng J, Sun R, et al. (2005) Involvement of human natural killer cells in asthma pathogenesis: natural killer 2 cells in type 2 cytokine predominance. J Allergy Clin Immunol 115: 841–847.
[15]
Ozdemir O (2005) Type 2 natural killer cells in asthma? J Allergy Clin Immunol 116: 1165–1166.
[16]
Mesdaghi M, Vodjgani M, Salehi E, Hadjati J, Sarrafnejad A, et al. (2010) Natural killer cells in allergic rhinitis patients and nonatopic controls. Int Arch Allergy Immunol 153: 234–238.
[17]
El-Shazly AE, Lefebvre PP (2011) Modulation of NK cell autocrine-induced eosinophil chemotaxis by interleukin-15 and vitamin D(3): a possible NK-eosinophil crosstalk via IL-8 in the pathophysiology of allergic rhinitis. Mediators Inflamm 2011: 373589.
[18]
Korsgren M, Persson CG, Sundler F, Bjerke T, Hansson T, et al. (1999) Natural killer cells determine development of allergen-induced eosinophilic airway inflammation in mice. J Exp Med 189: 553–562.
[19]
Matsubara S, Takeda K, Kodama T, Joetham A, Miyahara N, et al. (2007) IL-2 and IL-18 attenuation of airway hyperresponsiveness requires STAT4, IFN gamma, and natural killer cells. Am J Respir Cell Mol Biol 36: 324–332.
[20]
Payne SC, Borish L, Steinke JW (2011) Genetics and phenotyping in chronic sinusitis. J Allergy Clin Immunol 128: 710–720.
[21]
Hamilos DL, Leung DY, Wood R, Cunningham L, Bean DK, et al. (1995) Evidence for distinct cytokine expression in allergic versus nonallergic chronic sinusitis. J Allergy Clin Immunol 96: 537–544.
[22]
Matsuwaki Y, Ookushi T, Asaka D, Mori E, Nakajima T, et al. (2008) Chronic rhinosinusitis: risk factors for the recurrence of chronic rhinosinusitis based on 5-year follow-up after endoscopic sinus surgery. Int Arch Allergy Immunol 146: S77–S81.
[23]
El-Shazly AE, Doloriert HC, Bisig B, Lefebvre PP, Delvenne P, et al. (2013) Novel cooperation between CX3CL1 and CCL26 inducing NK cell chemotaxis via CX3CR1: a possible mechanism for NK cell infiltration of the allergic nasal tissue. Clin Exp Allergy 43: 322–331.
[24]
Fokkens WJ (2010) Recalcitrant rhinosinusitis, the diagnosis and treatment and evaluation of results. Rhinology 48: 257–258.
[25]
Ombrello MJ, Remmers EF, Sun G, Freeman AF, Datta S, et al. (2012) Cold urticaria, immunodeficiency, and autoimmunity related to PLCG2 deletions. N Engl J Med 366: 330–338.
[26]
Kavathas P, Bach FH, DeMars R (1980) Gamma ray-induced loss of expression of HLA and glyoxalase I alleles in lymphoblastoid cells. Proc Natl Acad Sci U S A 77: 4251–4255.
[27]
Kim HS, Long EO (2012) Complementary Phosphorylation Sites in the Adaptor Protein SLP-76 Promote Synergistic Activation of Natural Killer Cells Sci Signal. 5: ra49.
[28]
Bryceson YT, March ME, Barber DF, Ljunggren HG, Long EO (2005) Cytolytic granule polarization and degranulation controlled by different receptors in resting NK cells. J Exp Med 202: 1001–1002.
[29]
Lopez-Vergès S, Milush JM, Pandey S, York VA, Arakawa-Hoyt J, et al. (2010) CD57 defines a functionally distinct population of mature NK cells in the human CD56dimCD16+ NK-cell subset. Blood 116: 3865–3874.
[30]
Hsu J, Peters AT (2011) Pathophysiology of chronic rhinosinusitis with nasal polyp. Am J Rhinol Allergy 25: 285–290.
[31]
Lodoen MB, Lanier LL (2006) Natural killer cells as an initial defense against pathogens. Curr Opin Immunol 18: 391–398.
[32]
Jiang D, Liang J, Hodge J, Lu B, Zhu Z, et al. (2004) Regulation of pulmonary fibrosis by chemokine receptor CXCR3. J Clin Invest 114: 291–299.
[33]
Strieter RM, Keane MP (2004) Innate immunity dictates cytokine polarization relevant to the development of pulmonary fibrosis. J Clin Invest 114: 165–168.
[34]
Lane AP, Truong-Tran QA, Schleimer RP (2006) Altered expression of genes associated with innate immunity and inflammation in recalcitrant rhinosinusitis with polyps. Am J Rhinol 20: 138–144.
[35]
Jyonouchi H, Sun S, Le H, Rimell FL (2001) Evidence of dysregulated cytokine production by sinus lavage and peripheral blood mononuclear cells in patients with treatment-resistant chronic rhinosinusitis. Arch Otolaryngol Head Neck Surg 127: 1488–1494.
[36]
Dupuy S, Lambert M, Zucman D, Choukem SP, Tognarelli S, et al. (2012) Human Herpesvirus 8 (HHV8) sequentially shapes the NK cell repertoire during the course of asymptomatic infection and Kaposi sarcoma. PLoS Pathog 8: e1002486.
[37]
Brandt CS, Baratin M, Yi EC, Kennedy J, Gao Z, et al. (2009) The B7 family member B7-H6 is a tumor cell ligand for the activating natural killer cell receptor NKp30 in humans. J Exp Med 206: 1495–1503.
[38]
Parolini S, Bottino C, Falco M, Augugliaro R, Giliani S, et al. (2000) X-linked lymphoproliferative disease. 2B4 molecules displaying inhibitory rather than activating function are responsible for the inability of natural killer cells to kill Epstein-Barr virus-infected cells. J Exp Med 192: 337–346.
[39]
Arnon TI, Lev M, Katz G, Chernobrov Y, Porgador A, et al. (2001) Recognition of viral hemagglutinins by NKp44 but not by NKp30. Eur J Immunol 31: 2680–2689.
[40]
Bresciani M, Paradis L, Des Roches A, Vernhet H, Vachier I, et al. (2001) Rhinosinusitis in severe asthma. J Allergy Clin Immunol 107: 73–80.
[41]
Papakosta D, Manika K, Kyriazis G, Kontakiotis T, Gioulekas D, et al. (2009) Bronchoalveolar lavage fluid eosinophils are correlated to natural killer cells in eosinophilic pneumonias. Respiration 78: 177–184.
