Eosinophils contribute to IL-4 production and shape the T-helper cytokine profile and inflammatory response in pulmonary cryptococcosis

American Journal of Pathology

Volumn 179, Issue 2, 2011, Pages 733-744

  Piehler, Daniel ^a   Stenzel, Werner ^b   Grahnert, Andreas ^a   Held, Josephin ^b   Richter, Lydia ^b   Köhler, Gabriele ^c   Richter, Tina ^a   Eschke, Maria ^a   Alber, Gottfried ^a   Mller, Uwe ^a  

^a UNIVERSITY OF LEIPZIG   (Germany)

^b CHARITÉ UNIVERSITÄTSMEDIZIN BERLIN   (Germany)

^c UNIVERSITY HOSPITAL MÜNSTER   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

GAMMA INTERFERON; INTERLEUKIN 33 RECEPTOR; INTERLEUKIN 4; INTERLEUKIN RECEPTOR; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CD4+ T LYMPHOCYTE; CELL MATURATION; CONTROLLED STUDY; CRYPTOCOCCUS NEOFORMANS; CYTOKINE PRODUCTION; CYTOKINE RESPONSE; EOSINOPHIL; FEMALE; IMMUNOREGULATION; INFLAMMATION; INFLAMMATORY CELL; MOUSE; NONHUMAN; PRIORITY JOURNAL; PULMONARY CRYPTOCOCCOSIS; TH1 CELL; TH17 CELL; TH2 CELL;

ANIMALS; CRYPTOCOCCOSIS; CRYPTOCOCCUS NEOFORMANS; ENZYME-LINKED IMMUNOSORBENT ASSAY; EOSINOPHILS; FEMALE; FLOW CYTOMETRY; IMMUNOGLOBULINS; IMMUNOHISTOCHEMISTRY; INFLAMMATION; INTERLEUKIN-4; LEUKOCYTES; LUNG DISEASES, FUNGAL; MICE; MICE, INBRED BALB C; STEM CELLS; T-LYMPHOCYTES, HELPER-INDUCER;

EID: 80052447493     PISSN: 00029440     EISSN: 15252191     Source Type: Journal    
DOI: 10.1016/j.ajpath.2011.04.025     Document Type: Article

References (81)

1. X. Lin, and J. Heitman The biology of the Cryptococcus neoformans species complex Annu Rev Microbiol 60 2006 69 105 (Pubitemid 44627941)
2. T.G. Mitchell, and J.R. Perfect Cryptococcosis in the era of AIDS: 100 years after the discovery of Cryptococcus neoformans Clin Microbiol Rev 8 1995 515 548
3. B.J. Park, K.A. Wannemuehler, B.J. Marston, N. Govender, P.G. Pappas, and T.M. Chiller Estimation of the current global burden of cryptococcal meningitis among persons living with HIV/AIDS AIDS 23 2009 525 530
4. M. Feldmesser, S. Tucker, and A. Casadevall Intracellular parasitism of macrophages by Cryptococcus neoformans Trends Microbiol 9 2001 273 278 (Pubitemid 32522807)
5. K. Voelz, D.A. Lammas, and R.C. May Cytokine signaling regulates the outcome of intracellular macrophage parasitism by Cryptococcus neoformans Infect Immun 77 2009 3450 3457
6. K. Voelz, and R.C. May Cryptococcal interactions with the host immune system Eukaryot Cell 9 2010 835 846
7. K. Decken, G. Kohler, K. Palmer-Lehmann, A. Wunderlin, F. Mattner, J. Magram, M.K. Gately, and G. Alber Interleukin-12 is essential for a protective Th1 response in mice infected with Cryptococcus neoformans Infect Immun 66 1998 4994 5000 (Pubitemid 28453112)
8. K.A. Hoag, M.F. Lipscomb, A.A. Izzo, and N.E. Street IL-12 and IFN-gamma are required for initiating the protective Th1 response to pulmonary cryptococcosis in resistant C.B-17 mice Am J Respir Cell Mol Biol 17 1997 733 739 (Pubitemid 127348664)
9. M.A. Kleinschek, U. Muller, N. Schutze, R. Sabat, R.K. Straubinger, W.M. Blumenschein, T. McClanahan, R.A. Kastelein, and G. Alber Administration of IL-23 engages innate and adaptive immune mechanisms during fungal infection Int Immunol 22 2010 81 90
10. G.B. Huffnagle, M.B. Boyd, N.E. Street, and M.F. Lipscomb IL-5 is required for eosinophil recruitment, crystal deposition, and mononuclear cell recruitment during a pulmonary Cryptococcus neoformans infection in genetically susceptible mice (C57BL/6) J Immunol 160 1998 2393 2400 (Pubitemid 28119923)
11. U. Muller, W. Stenzel, G. Kohler, C. Werner, T. Polte, G. Hansen, N. Schutze, R.K. Straubinger, M. Blessing, A.N. McKenzie, F. Brombacher, and G. Alber IL-13 induces disease-promoting type 2 cytokines, alternatively activated macrophages and allergic inflammation during pulmonary infection of mice with Cryptococcus neoformans J Immunol 179 2007 5367 5377
12. Y.C. Chang, M.F. Stins, M.J. McCaffery, G.F. Miller, D.R. Pare, T. Dam, M. Paul-Satyaseela, K.S. Kim, and K.J. Kwon-Chung Cryptococcal yeast cells invade the central nervous system via transcellular penetration of the blood-brain barrier Infect Immun 72 2004 4985 4995 (Pubitemid 39223381)
13. C. Charlier, F. Chretien, M. Baudrimont, E. Mordelet, O. Lortholary, and F. Dromer Capsule structure changes associated with Cryptococcus neoformans crossing of the blood-brain barrier Am J Pathol 166 2005 421 432 (Pubitemid 40189039)
14. C. Charlier, K. Nielsen, S. Daou, M. Brigitte, F. Chretien, and F. Dromer Evidence of a role for monocytes in dissemination and brain invasion by Cryptococcus neoformans Infect Immun 77 2009 120 127
15. W. Stenzel, U. Muller, G. Kohler, F.L. Heppner, M. Blessing, A.N. McKenzie, F. Brombacher, and G. Alber IL-4/IL-13-dependent alternative activation of macrophages but not microglial cells is associated with uncontrolled cerebral cryptococcosis Am J Pathol 174 2009 486 496
16. D.L. Goldman, H. Khine, J. Abadi, D.J. Lindenberg, L. Pirofski, R. Niang, and A. Casadevall Serologic evidence for Cryptococcus neoformans infection in early childhood Pediatrics 107 2001 E66
17. D.L. Goldman, J. Davis, F. Bommarito, X. Shao, and A. Casadevall Enhanced allergic inflammation and airway responsiveness in rats with chronic Cryptococcus neoformans infection: potential role for fungal pulmonary infection in the pathogenesis of asthma J Infect Dis 193 2006 1178 1186
18. U. Muller, W. Stenzel, G. Kohler, T. Polte, M. Blessing, A. Mann, D. Piehler, F. Brombacher, and G. Alber A gene-dosage effect for interleukin-4 receptor alpha-chain expression has an impact on Th2-mediated allergic inflammation during bronchopulmonary mycosis J Infect Dis 198 2008 1714 1721
19. J.J. Osterholzer, R. Surana, J.E. Milam, G.T. Montano, G.H. Chen, J. Sonstein, J.L. Curtis, G.B. Huffnagle, G.B. Toews, and M.A. Olszewski Cryptococcal urease promotes the accumulation of immature dendritic cells and a non-protective T2 immune response within the lung Am J Pathol 174 2009 932 943
20. M. Mohrs, K. Shinkai, K. Mohrs, and R.M. Locksley Analysis of type 2 immunity in vivo with a bicistronic IL-4 reporter Immunity 15 2001 303 311 (Pubitemid 32816878)
21. C. Yu, A.B. Cantor, H. Yang, C. Browne, R.A. Wells, Y. Fujiwara, and S.H. Orkin Targeted deletion of a high-affinity GATA-binding site in the GATA-1 promoter leads to selective loss of the eosinophil lineage in vivo J Exp Med 195 2002 1387 1395 (Pubitemid 34602816)
22. M.A. Kleinschek, U. Muller, S.J. Brodie, W. Stenzel, G. Kohler, W.M. Blumenschein, R.K. Straubinger, T. McClanahan, R.A. Kastelein, and G. Alber IL-23 enhances the inflammatory cell response in Cryptococcus neoformans infection and induces a cytokine pattern distinct from IL-12 J Immunol 176 2006 1098 1106 (Pubitemid 43099711)
23. M. Feldmesser, A. Casadevall, Y. Kress, G. Spira, and A. Orlofsky Eosinophil-Cryptococcus neoformans interactions in vivo and in vitro Infect Immun 65 1997 1899 1907 (Pubitemid 27193617)
24. Y. Hernandez, S. Arora, J.R. Erb-Downward, R.A. McDonald, G.B. Toews, and G.B. Huffnagle Distinct roles for IL-4 and IL-10 in regulating T2 immunity during allergic bronchopulmonary mycosis J Immunol 174 2005 1027 1036 (Pubitemid 40094299)
25. K. Kawakami, S. Kohno, N. Morikawa, J. Kadota, A. Saito, and K. Hara Activation of macrophages and expansion of specific T lymphocytes in the lungs of mice intratracheally inoculated with Cryptococcus neoformans Clin Exp Immunol 96 1994 230 237 (Pubitemid 24213828)
26. K. Kawakami, Y. Koguchi, M.H. Qureshi, A. Miyazato, S. Yara, Y. Kinjo, Y. Iwakura, K. Takeda, S. Akira, M. Kurimoto, and A. Saito IL-18 contributes to host resistance against infection with Cryptococcus neoformans in mice with defective IL-12 synthesis through induction of IFN-gamma production by NK cells J Immunol 165 2000 941 947 (Pubitemid 30484762)
27. K. Kawakami, M.H. Qureshi, T. Zhang, Y. Koguchi, S. Yara, K. Takeda, S. Akira, M. Kurimoto, and A. Saito Involvement of endogenously synthesized interleukin (IL)-18 in the protective effects of IL-12 against pulmonary infection with Cryptococcus neoformans in mice FEMS Immunol Med Microbiol 27 2000 191 200 (Pubitemid 30103697)
28. A. Gessner, K. Mohrs, and M. Mohrs Mast cells, basophils, and eosinophils acquire constitutive IL-4 and IL-13 transcripts during lineage differentiation that are sufficient for rapid cytokine production J Immunol 174 2005 1063 1072 (Pubitemid 40094303)
29. D. Voehringer, K. Shinkai, and R.M. Locksley Type 2 immunity reflects orchestrated recruitment of cells committed to IL-4 production Immunity 20 2004 267 277 (Pubitemid 38388229)
30. V. Pochanke, S. Koller, R. Dayer, S. Hatak, B. Ludewig, R.M. Zinkernagel, H. Hengartner, and K.D. McCoy Identification and characterization of a novel antigen from the nematode Nippostrongylus brasiliensis recognized by specific IgE Eur J Immunol 37 2007 1275 1284 (Pubitemid 46925312)
31. K. Shinkai, M. Mohrs, and R.M. Locksley Helper T cells regulate type-2 innate immunity in vivo Nature 420 2002 825 829 (Pubitemid 36019631)
32. W.E. Paul What determines Th2 differentiation, in vitro and in vivo? Immunol Cell Biol 88 2010 236 239
33. M. Lohning, A. Stroehmann, A.J. Coyle, J.L. Grogan, S. Lin, J.C. Gutierrez-Ramos, D. Levinson, A. Radbruch, and T. Kamradt T1/ST2 is preferentially expressed on murine Th2 cells, independent of interleukin 4, interleukin 5, and interleukin 10, and important for Th2 effector function Proc Natl Acad Sci U S A 95 1998 6930 6935 (Pubitemid 28278084)
34. G.B. Huffnagle, J.L. Yates, and M.F. Lipscomb Immunity to a pulmonary Cryptococcus neoformans infection requires both CD4+ and CD8+ T cells J Exp Med 173 1991 793 800
35. K. Kawakami, S. Kohno, J. Kadota, M. Tohyama, K. Teruya, N. Kudeken, A. Saito, and K. Hara T cell-dependent activation of macrophages and enhancement of their phagocytic activity in the lungs of mice inoculated with heat-killed Cryptococcus neoformans: involvement of IFN-gamma and its protective effect against cryptococcal infection Microbiol Immunol 39 1995 135 143
36. G.H. Chen, R.A. McDonald, J.C. Wells, G.B. Huffnagle, N.W. Lukacs, and G.B. Toews The gamma interferon receptor is required for the protective pulmonary inflammatory response to Cryptococcus neoformans Infect Immun 73 2005 1788 1796 (Pubitemid 40470768)
37. P.K. Chattopadhyay, J. Yu, and M. Roederer A live-cell assay to detect antigen-specific CD4+ T cells with diverse cytokine profiles Nat Med 11 2005 1113 1117 (Pubitemid 41486835)
38. M. Frentsch, O. Arbach, D. Kirchhoff, B. Moewes, M. Worm, M. Rothe, A. Scheffold, and A. Thiel Direct access to CD4+ T cells specific for defined antigens according to CD154 expression Nat Med 11 2005 1118 1124 (Pubitemid 41486836)
39. S. Arora, Y. Hernandez, J.R. Erb-Downward, R.A. McDonald, G.B. Toews, and G.B. Huffnagle Role of IFN-gamma in regulating T2 immunity and the development of alternatively activated macrophages during allergic bronchopulmonary mycosis J Immunol 174 2005 6346 6356 (Pubitemid 40663828)
40. Y. Zhang, F. Wang, U. Bhan, G.B. Huffnagle, G.B. Toews, T.J. Standiford, and M.A. Olszewski TLR9 signaling is required for generation of the adaptive immune protection in Cryptococcus neoformans-infected lungs Am J Pathol 177 2010 754 765
41. M. Feldmesser, Y. Kress, and A. Casadevall Intracellular crystal formation as a mechanism of cytotoxicity in murine pulmonary Cryptococcus neoformans infection Infect Immun 69 2001 2723 2727 (Pubitemid 32239750)
42. A.V. Jain, Y. Zhang, W.B. Fields, D.A. McNamara, M.Y. Choe, G.H. Chen, J. Erb-Downward, J.J. Osterholzer, G.B. Toews, G.B. Huffnagle, and M.A. Olszewski Th2 but not Th1 immune bias results in altered lung functions in a murine model of pulmonary Cryptococcus neoformans infection Infect Immun 77 2009 5389 5399
43. J. Rivera, and A. Casadevall Mouse genetic background is a major determinant of isotype-related differences for antibody-mediated protective efficacy against Cryptococcus neoformans J Immunol 174 2005 8017 8026 (Pubitemid 40806313)
44. R.K. Marwaha, A. Trehan, K. Jayashree, and R.K. Vasishta Hypereosinophilia in disseminated cryptococcal disease Pediatr Infect Dis J 14 1995 1102 1103 (Pubitemid 26008466)
45. H.Y. Sun, B.D. Alexander, O. Lortholary, F. Dromer, G.N. Forrest, G.M. Lyon, J. Somani, K.L. Gupta, B.R. Del, T.L. Pruett, C.D. Sifri, A.P. Limaye, G.T. John, G.B. Klintmalm, K. Pursell, V. Stosor, M.I. Morris, L.A. Dowdy, P. Munoz, A.C. Kalil, J. Garcia-Diaz, S.L. Orloff, A.A. House, S.H. Houston, D. Wray, S. Huprikar, L.B. Johnson, A. Humar, R.R. Razonable, R.A. Fisher, S. Husain, M.M. Wagener, and N. Singh Cutaneous cryptococcosis in solid organ transplant recipients Med Mycol 48 2010 785 791
46. H. Yamaguchi, Y. Komase, M. Ikehara, T. Yamamoto, and T. Shinagawa Disseminated cryptococcal infection with eosinophilia in a healthy person J Infect Chemother 14 2008 319 324
47. A.P. Garro, L.S. Chiapello, J.L. Baronetti, and D.T. Masih Rat eosinophils stimulate the expansion of Cryptococcus neoformans-specific CD4(+) and CD8(+) T cells with a T-helper 1 profile Immunology 132 2011 174 187
48. J.W. Murphy Protective cell-mediated immunity against Cryptococcus neoformans Res Immunol 149 1998 373 386 (Pubitemid 28372454)
49. P.C. Fulkerson, C.A. Fischetti, M.L. McBride, L.M. Hassman, S.P. Hogan, and M.E. Rothenberg A central regulatory role for eosinophils and the eotaxin/CCR3 axis in chronic experimental allergic airway inflammation Proc Natl Acad Sci U S A 103 2006 16418 16423 (Pubitemid 44715211)
50. J.G. Perrigoue, S.A. Saenz, M.C. Siracusa, E.J. Allenspach, B.C. Taylor, P.R. Giacomin, M.G. Nair, Y. Du, C. Zaph, R.N. Van, M.R. Comeau, E.J. Pearce, T.M. Laufer, and D. Artis MHC class II-dependent basophil-CD4+ T cell interactions promote T(H)2 cytokine-dependent immunity Nat Immunol 10 2009 697 705
51. T. Yoshimoto, K. Yasuda, H. Tanaka, M. Nakahira, Y. Imai, Y. Fujimori, and K. Nakanishi Basophils contribute to T(H)2-IgE responses in vivo via IL-4 production and presentation of peptide-MHC class II complexes to CD4+ T cells Nat Immunol 10 2009 706 712
52. C.L. Sokol, N.Q. Chu, S. Yu, S.A. Nish, T.M. Laufer, and R. Medzhitov Basophils function as antigen-presenting cells for an allergen-induced T helper type 2 response Nat Immunol 10 2009 713 720
53. K.M. Murphy, and S.L. Reiner The lineage decisions of helper T cells Nat Rev Immunol 2 2002 933 944 (Pubitemid 37323214)
54. J. Zhu, and W.E. Paul CD4 T cells: fates, functions, and faults Blood 112 2008 1557 1569
55. M.R. Comeau, and S.F. Ziegler The influence of TSLP on the allergic response Mucosal Immunol 3 2010 138 147
56. Y. Nagata, H. Kamijuku, M. Taniguchi, S. Ziegler, and K. Seino Differential role of thymic stromal lymphopoietin in the induction of airway hyperreactivity and Th2 immune response in antigen-induced asthma with respect to natural killer T cell function Int Arch Allergy Immunol 144 2007 305 314 (Pubitemid 350126514)
57. M. Omori, and S. Ziegler Induction of IL-4 expression in CD4(+) T cells by thymic stromal lymphopoietin J Immunol 178 2007 1396 1404 (Pubitemid 46154610)
58. Y.H. Wang, and Y.J. Liu Thymic stromal lymphopoietin, OX40-ligand, and interleukin-25 in allergic responses Clin Exp Allergy 39 2009 798 806
59. W.H. Boom, D. Liano, and A.K. Abbas Heterogeneity of helper/inducer T lymphocytes, II: effects of interleukin 4- and interleukin 2-producing T cell clones on resting B lymphocytes J Exp Med 167 1988 1350 1363
60. E.A. Kurt-Jones, S. Hamberg, J. Ohara, W.E. Paul, and A.K. Abbas Heterogeneity of helper/inducer T lymphocytes, I: lymphokine production and lymphokine responsiveness J Exp Med 166 1987 1774 1787 (Pubitemid 18000354)
61. H.M. Cherwinski, J.H. Schumacher, K.D. Brown, and T.R. Mosmann Two types of mouse helper T cell clone, III: further differences in lymphokine synthesis between Th1 and Th2 clones revealed by RNA hybridization, functionally monospecific bioassays, and monoclonal antibodies J Exp Med 166 1987 1229 1244 (Pubitemid 18051419)
62. D. Jankovic, M.C. Kullberg, N. Noben-Trauth, P. Caspar, W.E. Paul, and A. Sher Single cell analysis reveals that IL-4 receptor/Stat6 signaling is not required for the in vivo or in vitro development of CD4+ lymphocytes with a Th2 cytokine profile J Immunol 164 2000 3047 3055 (Pubitemid 30148964)
63. S.I. Ochkur, E.A. Jacobsen, C.A. Protheroe, T.L. Biechele, R.S. Pero, M.P. McGarry, H. Wang, K.R. O'Neill, D.C. Colbert, T.V. Colby, H. Shen, M.R. Blackburn, C.C. Irvin, J.J. Lee, and N.A. Lee Coexpression of IL-5 and eotaxin-2 in mice creates an eosinophil-dependent model of respiratory inflammation with characteristics of severe asthma J Immunol 178 2007 7879 7889 (Pubitemid 46898060)
64. N.A. Barrett, and K.F. Austen Innate cells and T helper 2 cell immunity in airway inflammation Immunity 31 2009 425 437
65. M.B. Headley, B. Zhou, W.X. Shih, T. Aye, M.R. Comeau, and S.F. Ziegler TSLP conditions the lung immune environment for the generation of pathogenic innate and antigen-specific adaptive immune responses J Immunol 182 2009 1641 1647
66. H. Hammad, M. Chieppa, F. Perros, M.A. Willart, R.N. Germain, and B.N. Lambrecht House dust mite allergen induces asthma via Toll-like receptor 4 triggering of airway structural cells Nat Med 15 2009 410 416
67. G.J. Gleich, E. Frigas, D.A. Loegering, D.L. Wassom, and D. Steinmuller Cytotoxic properties of the eosinophil major basic protein J Immunol 123 1979 2925 2927 (Pubitemid 10202545)
68. D.L. Wassom, and G.J. Gleich Damage to Trichinella spiralis newborn larvae by eosinophil major basic protein Am J Trop Med Hyg 28 1979 860 863 (Pubitemid 10244405)
69. A.E. Butterworth, M.A. Vadas, D.L. Wassom, A. Dessein, M. Hogan, B. Sherry, G.J. Gleich, and J.R. David Interactions between human eosinophils and schistosomula of Schistosoma mansoni, II: the mechanism of irreversible eosinophil adherence J Exp Med 150 1979 1456 1471 (Pubitemid 10168590)
70. S.N. Linch, A.M. Kelly, E.T. Danielson, R. Pero, J.J. Lee, and J.A. Gold Mouse eosinophils possess potent antibacterial properties in vivo Infect Immun 77 2009 4976 4982
71. S. Yousefi, J.A. Gold, N. Andina, J.J. Lee, A.M. Kelly, E. Kozlowski, I. Schmid, A. Straumann, J. Reichenbach, G.J. Gleich, and H.U. Simon Catapult-like release of mitochondrial DNA by eosinophils contributes to antibacterial defense Nat Med 14 2008 949 953
72. J.B. Domachowske, C.A. Bonville, K.D. Dyer, A.J. Easton, and H.F. Rosenberg Pulmonary eosinophilia and production of MIP-1alpha are prominent responses to infection with pneumonia virus of mice Cell Immunol 200 2000 98 104 (Pubitemid 30228259)
73. Y. Inoue, Y. Matsuwaki, S.H. Shin, J.U. Ponikau, and H. Kita Nonpathogenic, environmental fungi induce activation and degranulation of human eosinophils J Immunol 175 2005 5439 5447 (Pubitemid 41456430)
74. T. Ishikawa, M.C. Yu, and C.E. Arbesman Electron microscopic demonstration of phagocytosis of Candida albicans by human eosinophilic leukocytes J Allergy Clin Immunol 50 1972 183 187
75. S.S. Witkin, J. Jeremias, and W.J. Ledger Vaginal eosinophils and IgE antibodies to Candida albicans in women with recurrent vaginitis J Med Vet Mycol 27 1989 57 58 (Pubitemid 19153217)
76. J. Yoon, J.U. Ponikau, C.B. Lawrence, and H. Kita Innate antifungal immunity of human eosinophils mediated by a beta 2 integrin, CD11b J Immunol 181 2008 2907 2915
77. E.A. Jacobsen, A.G. Taranova, N.A. Lee, and J.J. Lee Eosinophils: singularly destructive effector cells or purveyors of immunoregulation? J Allergy Clin Immunol 119 2007 1313 1320 (Pubitemid 46855871)
78. M.E. Rothenberg, and S.P. Hogan The eosinophil Annu Rev Immunol 24 2006 147 174
79. C. Blanchard, and M.E. Rothenberg Biology of the eosinophil Adv Immunol 101 2009 81 121
80. E.A. Jacobsen, S.I. Ochkur, R.S. Pero, A.G. Taranova, C.A. Protheroe, D.C. Colbert, N.A. Lee, and J.J. Lee Allergic pulmonary inflammation in mice is dependent on eosinophil-induced recruitment of effector T cells J Exp Med 205 2008 699 710 (Pubitemid 351439314)
81. J.J. Lee, E.A. Jacobsen, M.P. McGarry, R.P. Schleimer, and N.A. Lee Eosinophils in health and disease: the LIAR hypothesis Clin Exp Allergy 40 2010 563 575