Mouse cytomegalovirus infection in BALB/c mice resembles virus-associated secondary hemophagocytic lymphohistiocytosis and shows a pathogenesis distinct from primary hemophagocytic lymphohistiocytosis

Journal of Immunology

Volumn 196, Issue 7, 2016, Pages 3124-3134

  Brisse, Ellen ^a   Imbrechts, Maya ^a   Put, Karen ^a   Avau, Anneleen ^a   Mitera, Tania ^a   Berghmans, Nele ^a   Rutgeerts, Omer ^b   Waer, Mark ^b   Ninivaggi, Marisa ^c   Kelchtermans, Hilde ^c   Boon, Louis ^d   Snoeck, Robert ^a   Wouters, Carine H ^e   Andrei, Graciela ^a   Matthys, Patrick ^a  

^a REGA INSTITUTE FOR MEDICAL RESEARCH   (Belgium)

^b UNIVERSITY OF LEUVEN   (Belgium)

^c MAASTRICHT UNIVERSITY   (Netherlands)

^d EPIRUS Biopharmaceuticals Netherlands BV   (Netherlands)

^e UNIVERSITY HOSPITALS LEUVEN   (Belgium)

Author keywords

[No Author keywords available]

Indexed keywords

GAMMA INTERFERON; INTERLEUKIN 2 RECEPTOR ALPHA; BIOLOGICAL MARKER; CYTOKINE;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BAGG ALBINO MOUSE; BLOOD CLOTTING DISORDER; BONE MARROW CELL; C57BL 6 MOUSE; CD8+ T LYMPHOCYTE; CONTROLLED STUDY; CYTOKINE STORM; CYTOMEGALOVIRUS INFECTION; CYTOPENIA; CYTOTOXICITY; ERYTHROPHAGOCYTOSIS; FEVER; HEMOPHAGOCYTIC SYNDROME; HYPERFERRITINEMIA; IMMUNOCOMPETENT CELL; LIVER DYSFUNCTION; LYMPHADENOPATHY; LYMPHOCYTE ACTIVATION; LYMPHOCYTE COUNT; LYMPHOID CELL; MOUSE; NATURAL KILLER CELL; NONHUMAN; PATHOGENESIS; PRIMARY HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS; PRIORITY JOURNAL; PROTEIN BLOOD LEVEL; SPLENOMEGALY; T CELL DEPLETION; VIRUS ASSOCIATED SECONDARY HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS; WILD TYPE; ANIMAL; COMPLICATION; DEFICIENCY; DISEASE MODEL; GENETICS; HERPES VIRUS INFECTION; HISTIOCYTE; IMMUNOLOGY; KNOCKOUT MOUSE; LIVER; LYMPHOHISTIOCYTOSIS, HEMOPHAGOCYTIC; METABOLISM; MUROMEGALOVIRUS; PATHOLOGY; PHYSIOLOGY; T LYMPHOCYTE SUBPOPULATION; VIROLOGY;

ANIMALS; BIOMARKERS; CYTOKINES; CYTOTOXICITY, IMMUNOLOGIC; DISEASE MODELS, ANIMAL; HERPESVIRIDAE INFECTIONS; HISTIOCYTES; INTERFERON-GAMMA; KILLER CELLS, NATURAL; LIVER; LYMPHOHISTIOCYTOSIS, HEMOPHAGOCYTIC; MICE; MICE, INBRED BALB C; MICE, KNOCKOUT; MUROMEGALOVIRUS; T-LYMPHOCYTE SUBSETS;

EID: 84962484453     PISSN: 00221767     EISSN: 15506606     Source Type: Journal    
DOI: 10.4049/jimmunol.1501035     Document Type: Article

References (65)

1. Janka, G. E. 2007. Familial and acquired hemophagocytic lymphohistiocytosis. Eur. J. Pediatr. 166:95-109.
2. Janka, G. E., and K. Lehmberg. 2013. Hemophagocytic lymphohistiocytosis: pathogenesis and treatment. Hematology Am. Soc. Hematol. Educ. Program 2013:605-611.
3. Walsh, C. M., M. Matloubian, C. C. Liu, R. Ueda, C. G. Kurahara, J. L. Christensen, M. T. Huang, J. D. Young, R. Ahmed, and W. R. Clark. 1994. Immune function in mice lacking the perforin gene. Proc. Natl. Acad. Sci. USA 91:10854-10858.
4. + T cells and interferon gamma are essential for the disorder. Blood 104:735-743.
5. Kögl, T., J. Müller, B. Jessen, A. Schmitt-Graeff, G. Janka, S. Ehl, U. Zur Stadt, and P. Aichele. 2013. Hemophagocytic lymphohistiocytosis in syntaxin-11-deficient mice: T-cell exhaustion limits fatal disease. Blood 121:604-613.
6. D'Orlando, O., F. Zhao, B. Kasper, Z. Orinska, J. Müller, I. Hermans-Borgmeyer, G. M. Griffiths, U. Zur Stadt, and S. Bulfone-Paus. 2013. Syntaxin 11 is required for NK and CD8. T-cell cytotoxicity and neutrophil degranulation. Eur. J. Immunol. 43:194-208.
7. Crozat, K., K. Hoebe, S. Ugolini, N. A. Hong, E. Janssen, S. Rutschmann, S. Mudd, S. Sovath, E. Vivier, and B. Beutler. 2007. Jinx, an MCMV susceptibility phenotype caused by disruption of Unc13d: a mouse model of type 3 familial hemophagocytic lymphohistiocytosis. J. Exp. Med. 204:853-863.
8. Pachlopnik Schmid, J., C.-H. Ho, J. Diana, G. Pivert, A. Lehuen, F. Geissmann, A. Fischer, and G. De Saint Basile. 2008. A Griscelli syndrome type 2 murine model of hemophagocytic lymphohistiocytosis (HLH). Eur. J. Immunol. 38:3219-3225.
9. Jessen, B., A. Maul-Pavicic, H. Ufheil, T. Vraetz, A. Enders, K. Lehmberg, A. Längler, U. Gross-Wieltsch, A. Bay, Z. Kaya, et al. 2011. Subtle differences in CTL cytotoxicity determine susceptibility to hemophagocytic lymphohistiocytosis in mice and humans with Chediak-Higashi syndrome. Blood 118:4620-4629.
10. Pachlopnik Schmid, J., C.-H. Ho, F. Chrétien, J. M. Lefebvre, G. Pivert, M. Kosco-Vilbois, W. Ferlin, F. Geissmann, A. Fischer, and G. De Saint Basile. 2009. Neutralization of IFNgamma defeats haemophagocytosis in LCMVinfected perforin- and Rab27a-deficient mice. EMBO Mol. Med. 1:112-124.
11. Zoller, E. E., J. E. Lykens, C. E. Terrell, J. Aliberti, A. H. Filipovich, P. M. Henson, and M. B. Jordan. 2011. Hemophagocytosis causes a consumptive anemia of inflammation. J. Exp. Med. 208:1203-1214.
12. Brown, D. E., M. W. McCoy, M. C. Pilonieta, R. N. Nix, and C. S. Detweiler. 2010. Chronic murine typhoid fever is a natural model of secondary hemophagocytic lymphohistiocytosis. PLoS One 5:e9441.
13. Strippoli, R., F. Carvello, R. Scianaro, L. De Pasquale, M. Vivarelli, S. Petrini, L. Bracci-Laudiero, and F. De Benedetti. 2012. Amplification of the response to Toll-like receptor ligands by prolonged exposure to interleukin-6 in mice: implication for the pathogenesis of macrophage activation syndrome. Arthritis Rheum. 64:1680-1688.
14. Behrens, E. M., S. W. Canna, K. Slade, S. Rao, P. A. Kreiger, M. Paessler, T. Kambayashi, and G. A. Koretzky. 2011. Repeated TLR9 stimulation results in macrophage activation syndrome-like disease in mice. J. Clin. Invest. 121:2264-2277.
15. Hayashi, K., N. Ohara, N. Teramoto, S. Onoda, H. L. Chen, T. Oka, E. Kondo, T. Yoshino, K. Takahashi, J. Yates, and T. Akagi. 2001. An animal model for human EBV-associated hemophagocytic syndrome: herpesvirus papio frequently induces fatal lymphoproliferative disorders with hemophagocytic syndrome in rabbits. Am. J. Pathol. 158:1533-1542.
16. Sato, K., N. Misawa, C. Nie, Y. Satou, D. Iwakiri, M. Matsuoka, R. Takahashi, K. Kuzushima, M. Ito, K. Takada, and Y. Koyanagi. 2011. A novel animal model of Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis in humanized mice. Blood 117:5663-5673.
17. Brisse, E., C. H. Wouters, and P. Matthys. 2015. Hemophagocytic lymphohistiocytosis (HLH): A heterogeneous spectrum of cytokine-driven immune disorders. Cytokine Growth Factor Rev. 26:263-280.
18. Canna, S. W., J. Wrobel, N. Chu, P. A. Kreiger, M. Paessler, and E. M. Behrens. 2013. Interferon-γ mediates anemia but is dispensable for fulminant toll-like receptor 9-induced macrophage activation syndrome and hemophagocytosis in mice. Arthritis Rheum. 65:1764-1775.
19. Canna, S. W., and E. M. Behrens. 2012. Not all hemophagocytes are created equally: appreciating the heterogeneity of the hemophagocytic syndromes. Curr. Opin. Rheumatol. 24:113-118.
20. Maakaroun, N. R., A. Moanna, J. T. Jacob, and H. Albrecht. 2010. Viral infections associated with haemophagocytic syndrome. Rev. Med. Virol. 20:93-105.
21. Rouphael, N. G., N. J. Talati, C. Vaughan, K. Cunningham, R. Moreira, and C. Gould. 2007. Infections associated with haemophagocytic syndrome. Lancet Infect. Dis. 7:814-822.
22. Ansuini, V., D. Rigante, and S. Esposito. 2013. Debate around infectiondependent hemophagocytic syndrome in paediatrics. BMC Infect. Dis. 13:15.
23. Ramos-Casals, M., P. Brito-Zerón, A. López-Guillermo, M. A. Khamashta, and X. Bosch. 2014. Adult haemophagocytic syndrome. Lancet 383:1503-1516.
24. Van Dommelen, S. L. H., N. Sumaria, R. D. Schreiber, A. A. Scalzo, M. J. Smyth, and M. A. Degli-Esposti. 2006. Perforin and granzymes have distinct roles in defensive immunity and immunopathology. Immunity 25:835-848.
25. Krmpotic, A., I. Bubic, B. Polic, P. Lucin, and S. Jonjic. 2003. Pathogenesis of murine cytomegalovirus infection. Microbes Infect. 5:1263-1277.
26. Corbett, A. J., J. D. Coudert, C. A. Forbes, and A. A. Scalzo. 2011. Functional consequences of natural sequence variation of murine cytomegalovirus m157 for Ly49 receptor specificity and NK cell activation. J. Immunol. 186:1713-1722.
27. Tagawa, Y., K. Sekikawa, and Y. Iwakura. 1997. Suppression of concanavalin A-induced hepatitis in IFN-gamma (-/-) mice, but not in TNF-alpha (-/-) mice: role for IFN-gamma in activating apoptosis of hepatocytes. J. Immunol. 159:1418-1428.
28. Ninivaggi, M., H. Kelchtermans, M. J. Kuijpers, B. Hemmeryckx, J. W. M. Heemskerk, T. Lindhout, M. F. Hoylaerts, and B. De Laat. 2014. Whole blood thrombin generation in Bmal1-deficient mice. Thromb. Haemost. 112:271-275.
29. Billiau, A. D., H. Sefrioui, L. Overbergh, O. Rutgeerts, J. Goebels, C. Mathieu, and M. Waer. 2001. Transforming growth factor-beta inhibits lymphokine activated killer cytotoxicity of bone marrow cells: implications for the graft-versusleukemia effect in irradiation allogeneic bone marrow chimeras. Transplantation 71:292-299.
30. Livak, K. J., and T. D. Schmittgen. 2001. Analysis of relative gene expression data using real-time quantitative PCR and the 2 (-Delta Delta C (T)) Method. Methods 25:402-408.
31. Santambrogio, P., A. Cozzi, S. Levi, E. Rovida, F. Magni, A. Albertini, and P. Arosio. 2000. Functional and immunological analysis of recombinant mouse H- and L-ferritins from Escherichia coli. Protein Expr. Purif. 19:212-218.
32. Henter, J. I., A. Horne, M. Arico, R. M. Egeler, D. Webb, J. Winiarski, and G. Janka. 2007. HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pedriatr. Blood Cancer 48:124-131.
33. Chan, C. B., M. Abe, N. Hashimoto, C. Hao, I. R. Williams, X. Liu, S. Nakao, A. Yamamoto, C. Zheng, J. I. Henter, et al. 2009. Mice lacking asparaginyl endopeptidase develop disorders resembling hemophagocytic syndrome. Proc. Natl. Acad. Sci. USA 106:468-473.
34. Green, R. M., and S. Flamm. 2002. AGA technical review on the evaluation of liver chemistry tests. Gastroenterology 123:1367-1384.
35. Bryceson, Y. T., D. Pende, A. Maul-Pavicic, K. C. Gilmour, H. Ufheil, T. Vraetz, S. C. Chiang, S. Marcenaro, R. Meazza, I. Bondzio, et al. 2012. A prospective evaluation of degranulation assays in the rapid diagnosis of familial hemophagocytic syndromes. Blood 119:2754-2763.
36. Aricò, M., M. Allen, S. Brusa, R. Clementi, D. Pende, R. Maccario, L. Moretta, and C. Danesino. 2002. Haemophagocytic lymphohistiocytosis: proposal of a diagnostic algorithm based on perforin expression. Br. J. Haematol. 119:180-188.
37. Grom, A. A., J. Villanueva, S. Lee, E. A. Goldmuntz, M. H. Passo, and A. Filipovich. 2003. Natural killer cell dysfunction in patients with systemiconset juvenile rheumatoid arthritis and macrophage activation syndrome. J. Pediatr. 142:292-296.
38. Alter, G., J. M. Malenfant, and M. Altfeld. 2004. CD107a as a functional marker for the identification of natural killer cell activity. J. Immunol. Methods 294:15-22.
39. Grom, A. A. 2004. Natural killer cell dysfunction: A common pathway in systemic-onset juvenile rheumatoid arthritis, macrophage activation syndrome, and hemophagocytic lymphohistiocytosis? Arthritis Rheum. 50:689-698.
40. Kogawa, K., S. M. Lee, J. Villanueva, D. Marmer, J. Sumegi, and A. H. Filipovich. 2002. Perforin expression in cytotoxic lymphocytes from patients with hemophagocytic lymphohistiocytosis and their family members. Blood 99:61-66.
41. Terrell, C. E., and M. B. Jordan. 2013. Perforin deficiency impairs a critical immunoregulatory loop involving murine CD8 (+) T cells and dendritic cells. Blood 121:5184-5191.
42. Lykens, J. E., C. E. Terrell, E. E. Zoller, K. Risma, and M. B. Jordan. 2011. Perforin is a critical physiologic regulator of T-cell activation. Blood 118:618-626.
43. Usmani, G. N., B. A. Woda, and P. E. Newburger. 2013. Advances in understanding the pathogenesis of HLH. Br. J. Haematol. 161:609-622.
44. Lambotte, O., P. Cacoub, N. Costedoat, G. Le Moel, Z. Amoura, and J.-C. Piette. 2003. High ferritin and low glycosylated ferritin may also be a marker of excessive macrophage activation. J. Rheumatol. 30:1027-1028.
45. Grom, A. A., and E. D. Mellins. 2010. Macrophage activation syndrome: advances towards understanding pathogenesis. Curr. Opin. Rheumatol. 22:561-566.
46. Rosário, C., G. Zandman-Goddard, E. G. Meyron-Holtz, D. P. D'Cruz, and Y. Shoenfeld. 2013. The hyperferritinemic syndrome: macrophage activation syndrome, Still's disease, septic shock and catastrophic antiphospholipid syndrome. BMC Med. 11:185.
47. Reddy, M., E. Eirikis, C. Davis, H. M. Davis, and U. Prabhakar. 2004. Comparative analysis of lymphocyte activation marker expression and cytokine secretion profile in stimulated human peripheral blood mononuclear cell cultures: an in vitro model to monitor cellular immune function. J. Immunol. Methods 293:127-142.
48. + lymphocytes and relationship to serum TNF-alpha, IFN-gamma, and sIL-2R levels in aging. Exp. Gerontol. 34:79-93.
49. Kaech, S. M., S. Hemby, E. Kersh, and R. Ahmed. 2002. Molecular and functional profiling of memory CD8 T cell differentiation. Cell 111:837-851.
50. Lanier, L. L., S. O'Fallon, C. Somoza, J. H. Phillips, P. S. Linsley, K. Okumura, D. Ito, and M. Azuma. 1995. CD80 (B7) and CD86 (B70) provide similar costimulatory signals for T cell proliferation, cytokine production, and generation of CTL. J. Immunol. 154:97-105.
51. Mazodier, K., V. Marin, D. Novick, C. Farnarier, S. Robitail, N. Schleinitz, V. Veit, P. Paul, M. Rubinstein, C. A. Dinarello, et al. 2005. Severe imbalance of IL-18/IL-18BP in patients with secondary hemophagocytic syndrome. Blood 106:3483-3489.
52. Osugi, Y., J. Hara, S. Tagawa, K. Takai, G. Hosoi, Y. Matsuda, H. Ohta, H. Fujisaki, M. Kobayashi, N. Sakata, et al. 1997. Cytokine production regulating Th1 and Th2 cytokines in hemophagocytic lymphohistiocytosis. Blood 89:4100-4103.
53. Fujiwara, F., S. Hibi, and S. Imashuku. 1993. Hypercytokinemia in hemophagocytic syndrome. Am. J. Pediatr. Hematol. Oncol. 15:92-98.
54. Billiau, A. D., T. Roskams, R. Van Damme-Lombaerts, P. Matthys, and C. Wouters. 2005. Macrophage activation syndrome: characteristic findings on liver biopsy illustrating the key role of activated, IFN-gamma-producing lymphocytes and IL-6- and TNF-alpha-producing macrophages. Blood 105:1648-1651.
55. Carr, J. M., M. McKinney, and J. McDonagh. 1989. Diagnosis of disseminated intravascular coagulation. Role of D-dimer. Am. J. Clin. Pathol. 91:280-287.
56. Jordan, M. B., C. E. Allen, S. Weitzman, A. H. Filipovich, and K. L. McClain. 2011. How I treat hemophagocytic lymphohistiocytosis. Blood 118:4041-4052.
57. Dalton, D., S. Pitts-Meek, S. Keshav, I. Figari, A. Bradley, and T. Stewart. 1993. Multiple defects of immune cell function in mice with disrupted interferongamma genes. Science 259:1739-1742.
58. Henter, J.-I., A. Ehrnst, J. Andersson, and G. Elinder. 1993. Familial hemophagocytic lymphohistiocytosis and viral infections. Acta Paediatr. 82:369-372.
59. Tabeta, K., P. Georgel, E. Janssen, X. Du, K. Hoebe, K. Crozat, S. Mudd, L. Shamel, S. Sovath, J. Goode, et al. 2004. Toll-like receptors 9 and 3 as essential components of innate immune defense against mouse cytomegalovirus infection. Proc. Natl. Acad. Sci. USA 101:3516-3521.
60. Teramura, T., Y. Tabata, T. Yagi, A. Morimoto, S. Hibi, and S. Imashuku. 2002. Quantitative analysis of cell-free Epstein-Barr virus genome copy number in patients with EBV-associated hemophagocytic lymphohistiocytosis. Leuk. Lymphoma 43:173-179.
61. Commins, S. P., L. Borish, and J. W. Steinke. 2010. Immunologic messenger molecules: cytokines, interferons, and chemokines. J. Allergy Clin. Immunol. 125 (2, Suppl. 2) S53-S72.
62. Kelchtermans, H., A. Billiau, and P. Matthys. 2008. How interferon-gamma keeps autoimmune diseases in check. Trends Immunol. 29:479-486.
63. Tesi, B., E. Sieni, C. Neves, F. Romano, V. Cetica, A. I. Cordeiro, S. Chiang, H. Schlums, L. Galli, S. Avenali, et al. 2015. Hemophagocytic lymphohistiocytosis in 2 patients with underlying IFN-γ receptor deficiency. J. Allergy Clin. Immunol. 135:1638-1641.
64. Yasumi, T., M. Hori, E. Hiejima, H. Shibata, K. Izawa, H. Oda, K. Yoshioka, K. Nakagawa, T. Kawai, R. Nishikomori, et al. 2015. Laboratory parameters identify familial haemophagocytic lymphohistiocytosis from other forms of paediatric haemophagocytosis. Br. J. Haematol. 170:532-538.
65. Krebs, P., K. Crozat, D. Popkin, M. B. Oldstone, and B. Beutler. 2011. Disruption of MyD88 signaling suppresses hemophagocytic lymphohistiocytosis in mice. Blood 117:6582-6588.