Analysis of the transcriptional networks underpinning the activation of murine macrophages by inflammatory mediators

Journal of Leukocyte Biology

Volumn 96, Issue 2, 2014, Pages 167-183

  Raza, Sobia ^a   Barnett, Mark W ^a   Barnett Itzhaki, Zohar ^b   Amit, Ido ^b   Hume, David A ^a   Freeman, Tom C ^a  

^a UNIVERSITY OF EDINBURGH   (United Kingdom)

^b WEIZMANN INSTITUTE OF SCIENCE   (Israel)

Author keywords

Gene expression; Interferon ; Interferon ; LPS

Indexed keywords

BETA INTERFERON; GAMMA INTERFERON; MAJOR HISTOCOMPATIBILITY ANTIGEN CLASS 2; MYELOID DIFFERENTIATION FACTOR 88; TOLL LIKE RECEPTOR 4; TRANSCRIPTION FACTOR;

ARTICLE; COMPLEMENT SYSTEM; CORRELATION ANALYSIS; DISEASE PREDISPOSITION; DISEASE RESISTANCE; FEEDBACK SYSTEM; GENE EXPRESSION; INNATE IMMUNITY; MACROPHAGE ACTIVATION; MALE; MEDIATOR; MOUSE; MOUSE STRAIN; NONHUMAN; PRIORITY JOURNAL; SIGNAL TRANSDUCTION; SYSTEMIC LUPUS ERYTHEMATOSUS; TRANSCRIPTION INITIATION;

GENE EXPRESSION; INTERFERON-Β; INTERFERON-Γ; LPS;

ANIMALS; GENE REGULATORY NETWORKS; HISTOCOMPATIBILITY ANTIGENS CLASS II; INFLAMMATION MEDIATORS; INTERFERON-BETA; INTERFERON-GAMMA; LIPOPOLYSACCHARIDES; MACROPHAGE ACTIVATION; MACROPHAGES; MALE; MICE; MICE, INBRED BALB C; MYELOID DIFFERENTIATION FACTOR 88; SIGNAL TRANSDUCTION; TOLL-LIKE RECEPTOR 4; TRANSCRIPTION, GENETIC;

EID: 84904993091     PISSN: 07415400     EISSN: 19383673     Source Type: Journal    
DOI: 10.1189/jlb.6HI0313-169R     Document Type: Article

References (84)

1. Pluddemann, A., Mukhopadhyay, S., Gordon, S. (2011) Innate immunity to intracellular pathogens: macrophage receptors and responses to microbial entry. Immunol. Rev. 240, 11-24.
2. Hume, D. A., Underhill, D. M., Sweet, M. J., Ozinsky, A. O., Liew, F. Y., Aderem, A. (2001) Macrophages exposed continuously to lipopolysaccharide and other agonists that act via Toll-like receptors exhibit a sustained and additive activation state. BMC Immunol. 2, 11.
3. Biswas, S. K., Chittezhath, M., Shalova, I. N., Lim, J. Y. (2012) Macrophage polarization and plasticity in health and disease. Immunol. Res. 53, 11-24.
4. Lu, Y. C., Yeh, W. C., Ohashi, P. S. (2008) LPS/TLR4 signal transduction pathway. Cytokine 42, 145-151.
5. Karaghiosoff, M., Steinborn, R., Kovarik, P., Kriegshauser, G., Baccarini, M., Donabauer, B., Reichart, U., Kolbe, T., Bogdan, C., Leanderson, T., Levy, D., Decker, T., Muller, M. (2003) Central role for type I interferons and Tyk2 in lipopolysaccharide-induced endotoxin shock. Nat. Immunol. 4, 471-477.
6. Thomas, K. E., Galligan, C. L., Newman, R. D., Fish, E. N., Vogel, S. N. (2006) Contribution of interferon-β to the murine macrophage response to the Toll-like receptor 4 agonist, lipopolysaccharide. J. Biol. Chem. 281, 31119-31130.
7. Medzhitov, R., Horng, T. (2009) Transcriptional control of the inflammatory response. Nat. Rev. Immunol. 9, 692-703.
8. Hargreaves, D. C., Horng, T., Medzhitov, R. (2009) Control of inducible gene expression by signal-dependent transcriptional elongation. Cell 138, 129-145.
9. Gilchrist, M., Thorsson, V., Li, B., Rust, A. G., Korb, M., Roach, J. C., Kennedy, K., Hai, T., Bolouri, H., Aderem, A. (2006) Systems biology approaches identify ATF3 as a negative regulator of Toll-like receptor 4. Nature 441, 173-178.
10. Nilsson, R., Bajic, V. B., Suzuki, H., di Bernardo, D., Bjorkegren, J., Katayama, S., Reid, J. F., Sweet, M. J., Gariboldi, M., Carninci, P., Hayashizaki, Y., Hume, D. A., Tegner, J., Ravasi, T. (2006) Transcriptional network dynamics in macrophage activation. Genomics 88, 133-142.
11. Boldrick, J. C., Alizadeh, A. A., Diehn, M., Dudoit, S., Liu, C. L., Belcher, C. E., Botstein, D., Staudt, L. M., Brown, P. O., Relman, D. A. (2002) Stereotyped and specific gene expression programs in human innate immune responses to bacteria. Proc. Natl. Acad. Sci. USA 99, 972-977.
12. Huang, H., Fletcher, A., Niu, Y., Wang, T. T., Yu, L. (2012) Characterization of lipopolysaccharide-stimulated cytokine expression in macrophages and monocytes. Inflamm Res. 61, 1329-1338.
13. Gioannini, T. L., Teghanemt, A., Zhang, D., Coussens, N. P., Dockstader, W., Ramaswamy, S., Weiss, J. P. (2004) Isolation of an endotoxin-MD-2 complex that produces Toll-like receptor 4-dependent cell activation at picomolar concentrations. Proc. Natl. Acad. Sci. USA 101, 4186-4191.
14. Haziot, A., Ferrero, E., Kontgen, F., Hijiya, N., Yamamoto, S., Silver, J., Stewart, C. L., Goyert, S. M. (1996) Resistance to endotoxin shock and reduced dissemination of gram-negative bacteria in CD14-deficient mice. Immunity 4, 407-414.
15. Costelloe, E. O., Stacey, K. J., Antalis, T. M., Hume, D. A. (1999) Regulation of the plasminogen activator inhibitor-2 (PAI-2) gene in murine macrophages. Demonstration of a novel pattern of responsiveness to bacterial endotoxin. J. Leukoc. Biol. 66, 172-182.
16. Mosser, D. M. (2003) The many faces of macrophage activation. J. Leukoc. Biol. 73, 209-212.
17. Schroder, K., Sweet, M. J., Hume, D. A. (2006) Signal integration between IFNγ and TLR signalling pathways in macrophages. Immunobiology 211, 511-524.
18. Liew, F. Y., Xu, D., Brint, E. K., O'Neill, L. A. (2005) Negative regulation of Toll-like receptor-mediated immune responses. Nat. Rev. Immunol. 5, 446-458.
19. Gessani, S., Belardelli, F., Pecorelli, A., Puddu, P., Baglioni, C. (1989) Bacterial lipopolysaccharide and β interferon induce transcription of β interferon mRNA and interferon secretion in murine macrophages. J. Virol. 63, 2785-2789.
20. Muller, U., Steinhoff, U., Reis, L. F., Hemmi, S., Pavlovic, J., Zinkernagel, R. M., Aguet, M. (1994) Functional role of type I and type II interferons in antiviral defense. Science 264, 1918-1921.
21. Van de Wetering, D., van Wengen, A., Savage, N. D., van de Vosse, E., van Dissel, J. T. (2011) IFN-γ cannot substitute lack of IFN-γ responsiveness in cells of an IFN-γR1 deficient patient. Clin. Immunol. 138, 282-290.
22. Heinz, S., Romanoski, C. E., Benner, C., Allison, K. A., Kaikkonen, M. U., Orozco, L. D., Glass, C. K. (2013) Effect of natural genetic variation on enhancer selection and function. Nature 503, 487-492.
23. Wells, C. A., Ravasi, T., Faulkner, G. J., Carninci, P., Okazaki, Y., Hayashizaki, Y., Sweet, M., Wainwright, B. J., Hume, D. A. (2003) Genetic control of the innate immune response. BMC Immunol. 4, 5.
24. Schroder, K., Irvine, K. M., Taylor, M. S., Bokil, N. J., Le Cao, K. A., Masterman, K. A., Labzin, L. I., Semple, C. A., Kapetanovic, R., Fairbairn, L., Akalin, A., Faulkner, G. J., Baillie, J. K., Gongora, M., Daub, C. O., Kawaji, H., McLachlan, G. J., Goldman, N., Grimmond, S. M., Carninci, P., Suzuki, H., Hayashizaki, Y., Lenhard, B., Hume, D. A., Sweet, M. J. (2012) Conservation and divergence in Toll-like receptor 4-regulated gene expression in primary human versus mouse macrophages. Proc. Natl. Acad. Sci. USA 109, E944-E953.
25. Kapetanovic, R., Fairbairn, L., Beraldi, D., Sester, D. P., Archibald, A. L., Tuggle, C. K., Hume, D. A. (2012) Pig bone marrow-derived macrophages resemble human macrophages in their response to bacterial lipopolysaccharide. J. Immunol. 188, 3382-3394.
26. Mills, C. D., Kincaid, K., Alt, J. M., Heilman, M. J., Hill, A. M. (2000) M-1/M-2 macrophages and the Th1/Th2 paradigm. J. Immunol. 164, 6166-6173.
27. Zawatzky, R., Wurmbaeck, H., Falk, W., Homfeld, A. (1991) Endogenous interferon specifically regulates Newcastle disease virus-induced cytokine gene expression in mouse macrophages. J. Virol. 65, 4839-4846.
28. Schilling, E., El Chartouni, C., Rehli, M. (2009) Allele-specific DNA methylation in mouse strains is mainly determined by cis-acting sequences. Genome Res. 19, 2028-2035.
29. Van Erp, K., Dach, K., Koch, I., Heesemann, J., Hoffmann, R. (2006) Role of strain differences on host resistance and the transcriptional response of macrophages to infection with Yersinia enterocolitica. Physiol. Genomics 25, 75-84.
30. Sakthianandeswaren, A., Curtis, J. M., Elso, C., Kumar, B., Baldwin, T. M., Lopaticki, S., Kedzierski, L., Smyth, G. K., Foote, S. J., Handman, E. (2010) Fine mapping of Leishmania major susceptibility Locus lmr2 and evidence of a role for Fli1 in disease and wound healing. Infect. Immun. 78, 2734-2744.
31. Hume, D. A., Summers, K. M., Raza, S., Baillie, J. K., Freeman, T. C. (2010) Functional clustering and lineage markers: insights into cellular differentiation and gene function from large-scale microarray studies of purified primary cell populations. Genomics 95, 328-338.
32. Mabbott, N. A., Kenneth Baillie, J., Hume, D. A., Freeman, T. C. (2010) Meta-analysis of lineage-specific gene expression signatures in mouse leukocyte populations. Immunobiology 215, 724-736.
33. Sweet, M. J., Campbell, C. C., Sester, D. P., Xu, D., McDonald, R. C., Stacey, K. J., Hume, D. A., Liew, F. Y. (2002) Colony-stimulating factor-1 suppresses responses to CpG DNA and expression of Toll-like receptor 9 but enhances responses to lipopolysaccharide in murine macrophages. J. Immunol. 168, 392-399.
34. Freeman, T. C., Goldovsky, L., Brosch, M., van Dongen, S., Maziere, P., Grocock, R. J., Freilich, S., Thornton, J., Enright, A. J. (2007) Construction, visualisation, and clustering of transcription networks from microarray expression data. PLoS Comput. Biol. 3, 2032-2042.
35. Van Dongen, S., Abreu-Goodger, C. (2012) Using MCL to extract clusters from networks. Methods Mol. Biol. 804, 281-295.
36. Huang da, W., Sherman, B. T., Tan, Q., Kir, J., Liu, D., Bryant, D., Guo, Y., Stephens, R., Baseler, M. W., Lane, H. C., Lempicki, R. A. (2007) DAVID Bioinformatics Resources: expanded annotation database and novel algorithms to better extract biology from large gene lists. Nucleic Acids Res. 35, W169-W175.
37. Amit, I., Garber, M., Chevrier, N., Leite, A. P., Donner, Y., Eisenhaure, T., Guttman, M., Grenier, J. K., Li, W., Zuk, O., Schubert, L. A., Birditt, B., Shay, T., Goren, A., Zhang, X., Smith, Z., Deering, R., McDonald, R. C., Cabili, M., Bernstein, B. E., Rinn, J. L., Meissner, A., Root, D. E., Hacohen, N., Regev, A. (2009) Unbiased reconstruction of a mammalian transcriptional network mediating pathogen responses. Science 326, 257-263.
38. Garber, M., Yosef, N., Goren, A., Raychowdhury, R., Thielke, A., Guttman, M., Robinson, J., Minie, B., Chevrier, N., Itzhaki, Z., Blecher-Gonen, R., Bornstein, C., Amann-Zalcenstein, D., Weiner, A., Friedrich, D., Meldrim, J., Ram, O., Cheng, C., Gnirke, A., Fisher, S., Friedman, N., Wong, B., Bernstein, B. E., Nusbaum, C., Hacohen, N., Regev, A., Amit, I. (2012) A high-throughput chromatin immunoprecipitation approach reveals principles of dynamic gene regulation in mammals. Mol. Cell 47, 810-822.
39. Hume, D. A., Wells, C. A., Ravasi, T. (2007) Transcriptional regulatory networks in macrophages. Novartis Found. Symp. 281, 2-18.
40. Ravasi, T., Wells, C. A., Hume, D. A. (2007) Systems biology of transcription control in macrophages. Bioessays 29, 1215-1226.
41. Sester, D. P., Trieu, A., Brion, K., Schroder, K., Ravasi, T., Robinson, J. A., McDonald, R. C., Ripoll, V., Wells, C. A., Suzuki, H., Hayashizaki, Y., Stacey, K. J., Hume, D. A., Sweet, M. J. (2005) LPS regulates a set of genes in primary murine macrophages by antagonising CSF-1 action. Immunobiology 210, 97-107.
42. Rafiq, S., Frayling, T. M., Vyse, T. J., Cunninghame Graham, D. S., Eggleton, P. (2010) Assessing association of common variation in the C1Q gene cluster with systemic lupus erythematosus. Clin. Exp. Immunol. 161, 284-289.
43. Brambila-Tapia, A. J., Davalos-Rodriguez, I. P., Gamez-Nava, J. I., Gonzalez-Lopez, L., Medina-Diaz, J., Bernard-Medina, A. G., Salazar-Paramo, M. (2012) CD28 proximal promoter polymorphisms in systemic lupus erythematosus susceptibility. Rheumatol. Int. 32, 2165-2168.
44. Namjou, B., Sestak, A. L., Armstrong, D. L., Zidovetzki, R., Kelly, J. A., Jacob, N., Ciobanu, V., Kaufman, K. M., Ojwang, J. O., Ziegler, J., et al. (2009) High-density genotyping of STAT4 reveals multiple haplotypic associations with systemic lupus erythematosus in different racial groups. Arthritis Rheum. 60, 1085-1095.
45. Furnrohr, B. G., Wach, S., Kelly, J. A., Haslbeck, M., Weber, C. K., Stach, C. M., Hueber, A. J., Graef, D., Spriewald, B. M., Manger, K., et al. (2010) Polymorphisms in the Hsp70 gene locus are genetically associated with systemic lupus erythematosus. Ann. Rheum. Dis. 69, 1983-1989.
46. Kim, J. R., Mathew, S. O., Patel, R. K., Pertusi, R. M., Mathew, P. A. (2010) Altered expression of signalling lymphocyte activation molecule (SLAM) family receptors CS1 (CD319) and 2B4 (CD244) in patients with systemic lupus erythematosus. Clin. Exp. Immunol. 160, 348-358.
47. Ota, Y., Kawaguchi, Y., Takagi, K., Tochimoto, A., Kawamoto, M., Katsumata, Y., Gono, T., Masuda, I., Ikari, K., Momohara, S., Yamanaka, H. (2010) Single nucleotide polymorphisms of CD244 gene predispose to renal and neuropsychiatric manifestations with systemic lupus erythematosus. Mod. Rheumatol. 20, 427-431.
48. Pontillo, A., Girardelli, M., Kamada, A. J., Pancotto, J. A., Donadi, E. A., Crovella, S., Sandrin-Garcia, P. (2012) Polimorphisms in inflammasome genes are involved in the predisposition to systemic lupus erythematosus. Autoimmunity 45, 271-278.
49. Dembic, Z., Ayane, M., Klein, J., Steinmetz, M., Benoist, C. O., Mathis, D. J. (1985) Inbred and wild mice carry identical deletions in their E α MHC genes. EMBO J. 4, 127-131.
50. Mathis, D. J., Benoist, C., Williams II, V. E., Kanter, M., McDevitt, H. O. (1983) Several mechanisms can account for defective E α gene expression in different mouse haplotypes. Proc. Natl. Acad. Sci. USA 80, 273-277.
51. Tulone, C., Tsang, J., Prokopowicz, Z., Grosvenor, N., Chain, B. (2007) Natural cathepsin E deficiency in the immune system of C57BL/6J mice. Immunogenetics 59, 927-935.
52. Ostuni, R., Piccolo, V., Barozzi, I., Polletti, S., Termanini, A., Bonifacio, S., Curina, A., Prosperini, E., Ghisletti, S., Natoli, G. (2013) Latent enhancers activated by stimulation in differentiated cells. Cell 152, 157-171.
53. Bhatt, D. M., Pandya-Jones, A., Tong, A. J., Barozzi, I., Lissner, M. M., Natoli, G., Black, D. L., Smale, S. T. (2012) Transcript dynamics of proinflammatory genes revealed by sequence analysis of subcellular RNA fractions. Cell 150, 279-290.
54. Iglesias, M. J., Reilly, S. J., Emanuelsson, O., Sennblad, B., Pirmoradian Najafabadi, M., Folkersen, L., Malarstig, A., Lagergren, J., Eriksson, P., Hamsten, A., Odeberg, J. (2012) Combined chromatin and expression analysis reveals specific regulatory mechanisms within cytokine genes in the macrophage early immune response. PLoS One 7, e32306.
55. Ghisletti, S., Barozzi, I., Mietton, F., Polletti, S., De Santa, F., Venturini, E., Gregory, L., Lonie, L., Chew, A., Wei, C. L., Ragoussis, J., Natoli, G. (2010) Identification and characterization of enhancers controlling the inflammatory gene expression program in macrophages. Immunity 32, 317-328.
56. Stolovitzky, G. A., Kundaje, A., Held, G. A., Duggar, K. H., Haudenschild, C. D., Zhou, D., Vasicek, T. J., Smith, K. D., Aderem, A., Roach, J. C. (2005) Statistical analysis of MPSS measurements: application to the study of LPS-activated macrophage gene expression. Proc. Natl. Acad. Sci. USA 102, 1402-1407.
57. Gao, J. J., Diesl, V., Wittmann, T., Morrison, D. C., Ryan, J. L., Vogel, S. N., Follettie, M. T. (2002) Regulation of gene expression in mouse macrophages stimulated with bacterial CpG-DNA and lipopolysaccharide. J. Leukoc. Biol. 72, 1234-1245.
58. Edwards, J. P., Zhang, X., Frauwirth, K. A., Mosser, D. M. (2006) Biochemical and functional characterization of three activated macrophage populations. J. Leukoc. Biol. 80, 1298-1307.
59. Fang, F. C. (2004) Antimicrobial reactive oxygen and nitrogen species: concepts and controversies. Nat. Rev. Microbiol. 2, 820-832.
60. Lloyd-Jones, K. L., Kelly, M. M., Kubes, P. (2008) Varying importance of soluble and membrane CD14 in endothelial detection of lipopolysaccharide. J. Immunol. 181, 1446-1453.
61. O'Neill, L. A., Bowie, A. G. (2007) The family of five: TIR-domain-containing adaptors in Toll-like receptor signalling. Nat. Rev. Immunol. 7, 353-364.
62. Didierlaurent, A., Brissoni, B., Velin, D., Aebi, N., Tardivel, A., Kaslin, E., Sirard, J. C., Angelov, G., Tschopp, J., Burns, K. (2006) Tollip regulates proinflammatory responses to interleukin-1 and lipopolysaccharide. Mol. Cell. Biol. 26, 735-742.
63. Sun, B., Rizzo, L. V., Sun, S. H., Chan, C. C., Wiggert, B., Wilder, R. L., Caspi, R. R. (1997) Genetic susceptibility to experimental autoimmune uveitis involves more than a predisposition to generate a T helper-1-like or a T helper-2-like response. J. Immunol. 159, 1004-1011.
64. Gueders, M. M., Paulissen, G., Crahay, C., Quesada-Calvo, F., Hacha, J., Van Hove, C., Tournoy, K., Louis, R., Foidart, J. M., Noel, A., Cataldo, D. D. (2009) Mouse models of asthma: a comparison between C57BL/6 and BALB/c strains regarding bronchial responsiveness, inflammation, and cytokine production. Inflamm. Res. 58, 845-854.
65. Wynn, T. A. (2004) Fibrotic disease and the T(H)1/T(H)2 paradigm. Nat. Rev. Immunol. 4, 583-594.
66. DeMaeyer, E., DeMaeyer-Guignard, J., Bailey, D. W. (1975) Effect of mouse genotype on interferon production. I. Lines congenic at the If-1 locus. Immunogenetics 1, 438-443.
67. Banchereau, J., Pascual, V. (2006) Type I interferon in systemic lupus erythematosus and other autoimmune diseases. Immunity 25, 383-392.
68. Bennett, L., Palucka, A. K., Arce, E., Cantrell, V., Borvak, J., Banchereau, J., Pascual, V. (2003) Interferon and granulopoiesis signatures in systemic lupus erythematosus blood. J. Exp. Med. 197, 711-723.
69. Hume, D. A. (2008) Macrophages as APC and the dendritic cell myth. J. Immunol. 181, 5829-5835.
70. Der, S. D., Zhou, A., Williams, B. R., Silverman, R. H. (1998) Identification of genes differentially regulated by interferon α, β, or γ using oligonucleotide arrays. Proc. Natl. Acad. Sci. USA 95, 15623-15628.
71. Indraccolo, S., Pfeffer, U., Minuzzo, S., Esposito, G., Roni, V., Mandruzzato, S., Ferrari, N., Anfosso, L., Dell'Eva, R., Noonan, D. M., Chieco-Bianchi, L., Albini, A., Amadori, A. (2007) Identification of genes selectively regulated by IFNs in endothelial cells. J. Immunol. 178, 1122-1135.
72. Waddell, S. J., Popper, S. J., Rubins, K. H., Griffiths, M. J., Brown, P. O., Levin, M., Relman, D. A. (2010) Dissecting interferon-induced transcriptional programs in human peripheral blood cells. PLoS One 5, e9753.
73. Zhang, S., Kim, C. C., Batra, S., McKerrow, J. H., Loke, P. (2010) Delineation of diverse macrophage activation programs in response to intracellular parasites and cytokines. PLoS Negl. Trop. Dis. 4, e648.
74. Negishi, H., Ohba, Y., Yanai, H., Takaoka, A., Honma, K., Yui, K., Matsuyama, T., Taniguchi, T., Honda, K. (2005) Negative regulation of Toll-like-receptor signaling by IRF-4. Proc. Natl. Acad. Sci. USA 102, 15989-15994.
75. Salojin, K. V., Owusu, I. B., Millerchip, K. A., Potter, M., Platt, K. A., Oravecz, T. (2006) Essential role of MAPK phosphatase-1 in the negative control of innate immune responses. J. Immunol. 176, 1899-1907.
76. Liu, G., Friggeri, A., Yang, Y., Park, Y. J., Tsuruta, Y., Abraham, E. (2009) miR-147, a microRNA that is induced upon Toll-like receptor stimulation, regulates murine macrophage inflammatory responses. Proc. Natl. Acad. Sci. USA 106, 15819-15824.
77. Becker, S., Devlin, R. B., Haskill, J. S. (1989) Differential production of tumor necrosis factor, macrophage colony stimulating factor, and interleukin 1 by human alveolar macrophages. J. Leukoc. Biol. 45, 353-361.
78. Liang, J., Song, W., Tromp, G., Kolattukudy, P. E., Fu, M. (2008) Genome-wide survey and expression profiling of CCCH-zinc finger family reveals a functional module in macrophage activation. PLoS One 3, e2880.
79. Mantovani, A., Sica, A., Sozzani, S., Allavena, P., Vecchi, A., Locati, M. (2004) The chemokine system in diverse forms of macrophage activation and polarization. Trends Immunol. 25, 677-686.
80. Krausgruber, T., Blazek, K., Smallie, T., Alzabin, S., Lockstone, H., Sahgal, N., Hussell, T., Feldmann, M., Udalova, I. A. (2011) IRF5 promotes inflammatory macrophage polarization and TH1-TH17 responses. Nat. Immunol. 12, 231-238.
81. Lombardo, E., Alvarez-Barrientos, A., Maroto, B., Bosca, L., Knaus, U. G. (2007) TLR4-mediated survival of macrophages is MyD88 dependent and requires TNF-α autocrine signalling. J. Immunol. 178, 3731-3739.
82. Gordon, S. (2003) Alternative activation of macrophages. Nat. Rev. Immunol. 3, 23-35.
83. Mosser, D. M., Edwards, J. P. (2008) Exploring the full spectrum of macrophage activation. Nat. Rev. Immunol. 8, 958-969.
84. Keane, T. M., Goodstadt, L., Danecek, P., White, M. A., Wong, K., Yalcin, B., Heger, A., Agam, A., Slater, G., Goodson, M., et al. (2011) Mouse genomic variation and its effect on phenotypes and gene regulation. Nature 477, 289-294.