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PLOS ONE  2014 

Colonic Immune Suppression, Barrier Dysfunction, and Dysbiosis by Gastrointestinal Bacillus anthracis Infection

DOI: 10.1371/journal.pone.0100532

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Abstract:

Gastrointestinal (GI) anthrax results from the ingestion of Bacillus anthracis. Herein, we investigated the pathogenesis of GI anthrax in animals orally infected with toxigenic non-encapsulated B. anthracis Sterne strain (pXO1+ pXO2?) spores that resulted in rapid animal death. B. anthracis Sterne induced significant breakdown of intestinal barrier function and led to gut dysbiosis, resulting in systemic dissemination of not only B. anthracis, but also of commensals. Disease progression significantly correlated with the deterioration of innate and T cell functions. Our studies provide critical immunologic and physiologic insights into the pathogenesis of GI anthrax infection, whereupon cleavage of mitogen-activated protein kinases (MAPKs) in immune cells may play a central role in promoting dysfunctional immune responses against this deadly pathogen.

References

[1]  Beatty ME, Ashford DA, Griffin PM, Tauxe RV, Sobel J (2003) Gastrointestinal anthrax: review of the literature. Arch Intern Med 163: 2527–2531. doi: 10.1001/archinte.163.20.2527
[2]  Mock M, Fouet A (2001) Anthrax. Annu Rev Microbiol 55: 647–671. doi: 10.1146/annurev.micro.55.1.647
[3]  Turnbull PC (1991) Anthrax vaccines: past, present and future. Vaccine 9: 533–539. doi: 10.1016/0264-410x(91)90237-z
[4]  Mikesell P, Ivins BE, Ristroph JD, Dreier TM (1983) Evidence for plasmid-mediated toxin production in Bacillus anthracis. Infect Immun 39: 371–376.
[5]  Green BD, Battisti L, Koehler TM, Thorne CB, Ivins BE (1985) Demonstration of a capsule plasmid in Bacillus anthracis. Infect Immun 49: 291–297.
[6]  Tonello F, Zornetta I (2012) Bacillus anthracis factors for phagosomal escape. Toxins (Basel) 4: 536–553. doi: 10.3390/toxins4070536
[7]  Makino S, Watarai M, Cheun HI, Shirahata T, Uchida I (2002) Effect of the lower molecular capsule released from the cell surface of Bacillus anthracis on the pathogenesis of anthrax. J Infect Dis 186: 227–233. doi: 10.1086/341299
[8]  Scorpio A, Chabot DJ, Day WA, O'Brien D K, Vietri NJ, et al. (2007) Poly-gamma-glutamate capsule-degrading enzyme treatment enhances phagocytosis and killing of encapsulated Bacillus anthracis. Antimicrobial agents and chemotherapy 51: 215–222. doi: 10.1128/aac.00706-06
[9]  Mohamadzadeh M, Duong T, Sandwick SJ, Hoover T, Klaenhammer TR (2009) Dendritic cell targeting of Bacillus anthracis protective antigen expressed by Lactobacillus acidophilus protects mice from lethal challenge. Proc Natl Acad Sci U S A 106: 4331–4336. doi: 10.1073/pnas.0900029106
[10]  Tournier JN, Ulrich RG, Quesnel-Hellmann A, Mohamadzadeh M, Stiles BG (2009) Anthrax, toxins and vaccines: a 125-year journey targeting Bacillus anthracis. Expert Rev Anti Infect Ther 7: 219–236. doi: 10.1586/14787210.7.2.219
[11]  Glomski IJ, Piris-Gimenez A, Huerre M, Mock M, Goossens PL (2007) Primary involvement of pharynx and peyer's patch in inhalational and intestinal anthrax. PLoS Pathog 3: e76. doi: 10.1371/journal.ppat.0030076
[12]  Tonry JH, Popov SG, Narayanan A, Kashanchi F, Hakami RM, et al. (2013) In vivo murine and in vitro M-like cell models of gastrointestinal anthrax. Microbes Infect 15: 37–44. doi: 10.1016/j.micinf.2012.10.004
[13]  Xie T, Sun C, Uslu K, Auth RD, Fang H, et al. (2013) A New Murine Model for Gastrointestinal Anthrax Infection. PLoS One 8: e66943. doi: 10.1371/journal.pone.0066943
[14]  Baldari CT, Tonello F, Paccani SR, Montecucco C (2006) Anthrax toxins: A paradigm of bacterial immune suppression. Trends in immunology 27: 434–440. doi: 10.1016/j.it.2006.07.002
[15]  Welkos SL, Keener TJ, Gibbs PH (1986) Differences in susceptibility of inbred mice to Bacillus anthracis. Infect Immun 51: 795–800.
[16]  Cheng SX (2012) Calcium-sensing receptor inhibits secretagogue-induced electrolyte secretion by intestine via the enteric nervous system. Am J Physiol Gastrointest Liver Physiol 303: G60–70. doi: 10.1152/ajpgi.00425.2011
[17]  Barman M, Unold D, Shifley K, Amir E, Hung K, et al. (2008) Enteric salmonellosis disrupts the microbial ecology of the murine gastrointestinal tract. Infect Immun 76: 907–915. doi: 10.1128/iai.01432-07
[18]  Antharam VC, Li EC, Ishmael A, Sharma A, Mai V, et al. (2013) Intestinal dysbiosis and depletion of butyrogenic bacteria in Clostridium difficile infection and nosocomial diarrhea. J Clin Microbiol 51: 2884–2892. doi: 10.1128/jcm.00845-13
[19]  Goossens PL (2009) Animal models of human anthrax: the Quest for the Holy Grail. Mol Aspects Med 30: 467–480. doi: 10.1016/j.mam.2009.07.005
[20]  Loving CL, Kennett M, Lee GM, Grippe VK, Merkel TJ (2007) Murine aerosol challenge model of anthrax. Infect Immun 75: 2689–2698. doi: 10.1128/iai.01875-06
[21]  Welkos SL, Keener TJ, Gibbs PH (1986) Differences in susceptibility of inbred mice to Bacillus anthracis. Infection and immunity 51: 795–800.
[22]  Salzman NH, Hung K, Haribhai D, Chu H, Karlsson-Sjoberg J, et al. (2010) Enteric defensins are essential regulators of intestinal microbial ecology. Nature immunology 11: 76–83. doi: 10.1038/ni.1825
[23]  Lozupone C, Lladser ME, Knights D, Stombaugh J, Knight R (2011) UniFrac: an effective distance metric for microbial community comparison. ISME J 5: 169–172. doi: 10.1038/ismej.2010.133
[24]  Segata N, Izard J, Waldron L, Gevers D, Miropolsky L, et al. (2011) Metagenomic biomarker discovery and explanation. Genome Biol 12: R60. doi: 10.1186/gb-2011-12-6-r60
[25]  Lau SK, Woo PC, Woo GK, Fung AM, Ngan AH, et al. (2006) Bacteraemia caused by Anaerotruncus colihominis and emended description of the species. J Clin Pathol 59: 748–752. doi: 10.1136/jcp.2005.031773
[26]  Hill JE, Fernando WM, Zello GA, Tyler RT, Dahl WJ, et al. (2010) Improvement of the representation of bifidobacteria in fecal microbiota metagenomic libraries by application of the cpn60 universal primer cocktail. Appl Environ Microbiol 76: 4550–4552. doi: 10.1128/aem.01510-09
[27]  Hu H, Leppla SH (2009) Anthrax toxin uptake by primary immune cells as determined with a lethal factor-beta-lactamase fusion protein. PloS one 4: e7946. doi: 10.1371/journal.pone.0007946
[28]  Agrawal A, Lingappa J, Leppla SH, Agrawal S, Jabbar A, et al. (2003) Impairment of dendritic cells and adaptive immunity by anthrax lethal toxin. Nature 424: 329–334. doi: 10.1038/nature01794
[29]  Duesbery NS, Webb CP, Leppla SH, Gordon VM, Klimpel KR, et al. (1998) Proteolytic inactivation of MAP-kinase-kinase by anthrax lethal factor. Science 280: 734–737. doi: 10.1126/science.280.5364.734
[30]  Vitale G, Bernardi L, Napolitani G, Mock M, Montecucco C (2000) Susceptibility of mitogen-activated protein kinase kinase family members to proteolysis by anthrax lethal factor. The Biochemical journal 352 Pt 3: 739–745. doi: 10.1042/0264-6021:3520739
[31]  Ebrahimi CM, Sheen TR, Renken CW, Gottlieb RA, Doran KS (2011) Contribution of lethal toxin and edema toxin to the pathogenesis of anthrax meningitis. Infection and immunity 79: 2510–2518. doi: 10.1128/iai.00006-11
[32]  Xie T, Auth RD, Frucht DM (2011) The effects of anthrax lethal toxin on host barrier function. Toxins 3: 591–607. doi: 10.3390/toxins3060591
[33]  Xu L, Frucht DM (2007) Bacillus anthracis: a multi-faceted role for anthrax lethal toxin in thwarting host immune defenses. The international journal of biochemistry & cell biology 39: 20–24. doi: 10.1016/j.biocel.2006.08.010
[34]  Park JM, Greten FR, Li ZW, Karin M (2002) Macrophage apoptosis by anthrax lethal factor through p38 MAP kinase inhibition. Science 297: 2048–2051. doi: 10.1126/science.1073163
[35]  During RL, Li W, Hao B, Koenig JM, Stephens DS, et al. (2005) Anthrax lethal toxin paralyzes neutrophil actin-based motility. The Journal of infectious diseases 192: 837–845. doi: 10.1086/432516
[36]  Chou PJ, Newton CA, Perkins I, Friedman H, Klein TW (2008) Suppression of dendritic cell activation by anthrax lethal toxin and edema toxin depends on multiple factors including cell source, stimulus used, and function tested. DNA Cell Biol 27: 637–648. doi: 10.1089/dna.2008.0760
[37]  Karakhanova S, Meisel S, Ring S, Mahnke K, Enk AH (2010) ERK/p38 MAP-kinases and PI3K are involved in the differential regulation of B7-H1 expression in DC subsets. Eur J Immunol 40: 254–266. doi: 10.1002/eji.200939289
[38]  Chopra AP, Boone SA, Liang X, Duesbery NS (2003) Anthrax lethal factor proteolysis and inactivation of MAPK kinase. J Biol Chem 278: 9402–9406. doi: 10.1074/jbc.m211262200
[39]  Paccani SR, Benagiano M, Savino MT, Finetti F, Tonello F, et al. (2011) The adenylate cyclase toxin of Bacillus anthracis is a potent promoter of T(H)17 cell development. The Journal of allergy and clinical immunology 127: 1635–1637. doi: 10.1016/j.jaci.2010.12.1104
[40]  Datta SK, Sabet M, Nguyen KP, Valdez PA, Gonzalez-Navajas JM, et al. (2010) Mucosal adjuvant activity of cholera toxin requires Th17 cells and protects against inhalation anthrax. Proc Natl Acad Sci U S A 107: 10638–10643. doi: 10.1073/pnas.1002348107
[41]  Wherry EJ, Ha SJ, Kaech SM, Haining WN, Sarkar S, et al. (2007) Molecular signature of CD8+ T cell exhaustion during chronic viral infection. Immunity 27: 670–684. doi: 10.1016/j.immuni.2007.09.006
[42]  Bonecchi R, Bianchi G, Bordignon PP, D'Ambrosio D, Lang R, et al. (1998) Differential expression of chemokine receptors and chemotactic responsiveness of type 1 T helper cells (Th1s) and Th2s. J Exp Med 187: 129–134. doi: 10.1084/jem.187.1.129
[43]  Lacotte S, Brun S, Muller S, Dumortier H (2009) CXCR3, inflammation, and autoimmune diseases. Ann N Y Acad Sci 1173: 310–317. doi: 10.1111/j.1749-6632.2009.04813.x
[44]  Swartz MN (2001) Recognition and management of anthrax–an update. N Engl J Med 345: 1621–1626. doi: 10.1056/nejmra012892
[45]  Sun C, Fang H, Xie T, Auth RD, Patel N, et al. (2012) Anthrax lethal toxin disrupts intestinal barrier function and causes systemic infections with enteric bacteria. PLoS One 7: e33583. doi: 10.1371/journal.pone.0033583
[46]  Chandra RK (1996) Nutrition, immunity and infection: from basic knowledge of dietary manipulation of immune responses to practical application of ameliorating suffering and improving survival. Proc Natl Acad Sci U S A 93: 14304–14307. doi: 10.1073/pnas.93.25.14304
[47]  Coggeshall KM, Lupu F, Ballard J, Metcalf JP, James JA, et al. (2013) The sepsis model: an emerging hypothesis for the lethality of inhalation anthrax. Journal of cellular and molecular medicine 17: 914–920. doi: 10.1111/jcmm.12075
[48]  Kern J, Schneewind O (2010) BslA, the S-layer adhesin of B. anthracis, is a virulence factor for anthrax pathogenesis. Mol Microbiol 75: 324–332. doi: 10.1111/j.1365-2958.2009.06958.x
[49]  Manichanh C, Borruel N, Casellas F, Guarner F (2012) The gut microbiota in IBD. Nature reviews Gastroenterology & hepatology 9: 599–608. doi: 10.1038/nrgastro.2012.152
[50]  Ewaschuk JB, Diaz H, Meddings L, Diederichs B, Dmytrash A, et al. (2008) Secreted bioactive factors from Bifidobacterium infantis enhance epithelial cell barrier function. American journal of physiology Gastrointestinal and liver physiology 295: G1025–1034. doi: 10.1152/ajpgi.90227.2008
[51]  Biddle A SL, Blanchard J, Leschine S (2013) Untangling the Genetic Basis of Fibrolytic Specialization by Lachnospiraceae and Ruminococcaceae in Diverse Gut Communities. Diversity 5: 627–640. doi: 10.3390/d5030627
[52]  Thibault R, Blachier F, Darcy-Vrillon B, de Coppet P, Bourreille A, et al. (2010) Butyrate utilization by the colonic mucosa in inflammatory bowel diseases: a transport deficiency. Inflammatory bowel diseases 16: 684–695. doi: 10.1002/ibd.21108
[53]  Atarashi K, Tanoue T, Shima T, Imaoka A, Kuwahara T, et al. (2011) Induction of colonic regulatory T cells by indigenous Clostridium species. Science 331: 337–341. doi: 10.1126/science.1198469
[54]  Mohamadzadeh M, Chen L, Schmaljohn AL (2007) How Ebola and Marburg viruses battle the immune system. Nat Rev Immunol 7: 556–567. doi: 10.1038/nri2098
[55]  Gianchecchi E, Delfino DV, Fierabracci A (2013) Recent insights into the role of the PD-1/PD-L1 pathway in immunological tolerance and autoimmunity. Autoimmunity reviews.
[56]  Bachmann M, Dragoi C, Poleganov MA, Pfeilschifter J (2007) M (2007) Interleukin-18 directly activates T-bet expression and function via p38 mitogen-activated protein kinase and nuclear factor-?∫B in acute myeloid leukemia, ?ìderived predendritic KG-1 cells. Molecular Cancer Therapeutics 6: 723–731. doi: 10.1158/1535-7163.mct-06-0505
[57]  Kao C, Oestreich KJ, Paley MA, Crawford A, Angelosanto JM, et al. (2011) Transcription factor T-bet represses expression of the inhibitory receptor PD-1 and sustains virus-specific CD8+ T cell responses during chronic infection. Nature immunology 12: 663–671. doi: 10.1038/ni.2046
[58]  Qian Y, Deng J, Geng L, Xie H, Jiang G, et al. (2008) TLR4 signaling induces B7-H1 expression through MAPK pathways in bladder cancer cells. Cancer investigation 26: 816–821. doi: 10.1080/07357900801941852
[59]  Pepper M, Linehan JL, Pagan AJ, Zell T, Dileepan T, et al. (2010) Different routes of bacterial infection induce long-lived TH1 memory cells and short-lived TH17 cells. Nature immunology 11: 83–89. doi: 10.1038/ni.1826
[60]  Balhara J, Gounni AS (2012) The alveolar macrophages in asthma: a double-edged sword. Mucosal immunology 5: 605–609. doi: 10.1038/mi.2012.74
[61]  Tsuji NM, Kosaka A (2008) Oral tolerance: intestinal homeostasis and antigen-specific regulatory T cells. Trends in immunology 29: 532–540. doi: 10.1016/j.it.2008.09.002

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