The mechanism of phagosome escape by intracellular pathogens is an important step in the infectious cycle. During the establishment of anthrax, Bacillus anthracis undergoes a transient intracellular phase in which spores are engulfed by local phagocytes. Spores germinate inside phagosomes and grow to vegetative bacilli, which emerge from their resident intracellular compartments, replicate and eventually exit from the plasma membrane. During germination, B. anthracis secretes multiple factors that can help its resistance to the phagocytes. Here the possible role of B. anthracis toxins, phospholipases, antioxidant enzymes and capsules in the phagosomal escape and survival, is analyzed and compared with that of factors of other microbial pathogens involved in the same type of process.
References
[1]
Dixon, T.C.; Meselson, M.; Guillemin, J.; Hanna, P.C. Anthrax. N. Engl. J. Med. 1999, 341, 815–826, doi:10.1056/NEJM199909093411107. 10477781
Baldari, C.T.; Tonello, F.; Paccani, S.R.; Montecucco, C. Anthrax toxins: A paradigm of bacterial immune suppression. Trends Immunol. 2006, 27, 434–440, doi:10.1016/j.it.2006.07.002. 16861036
[4]
Ezzell, J.W.; Welkos, S.L. The capsule of bacillus anthracis, a review. J. Appl. Microbiol. 1999, 87, 250, doi:10.1046/j.1365-2672.1999.00881.x. 10475959
[5]
Ross, J.M. The pathogenesis of anthrax following the administration of spores by the respiratory route. J. Pathol. Bacteriol. 1957, 73, 485–494, doi:10.1002/path.1700730219.
[6]
Cote, C.K.; Welkos, S.L.; Bozue, J. Key aspects of the molecular and cellular basis of inhalational anthrax. Microbes Infect. 2011, 13, 1146–1155, doi:10.1016/j.micinf.2011.07.005. 21816231
[7]
Russell, B.H.; Vasan, R.; Keene, D.R.; Koehler, T.M.; Xu, Y. Potential dissemination of Bacillus anthracis utilizing human lung epithelial cells. Cell Microbiol. 2008, 10, 945–957, doi:10.1111/j.1462-5822.2007.01098.x.
[8]
Weiner, Z.P.; Glomski, I.J. Updating Perspectives on the Initiation of Bacillus anthracis Growth and Dissemination through Its Host. Infect. Immun. 2012, 80, 1626–1633, doi:10.1128/IAI.06061-11.
[9]
Oliva, C.; Turnbough, C.L.; Kearney, J.F. CD14-Mac-1 interactions in Bacillus anthracis spore internalization by macrophages. Proc. Natl. Acad. Sci. USA 2009, 106, 13957–13962, doi:10.1073/pnas.0902392106. 19666536
[10]
Oliva, C.R.; Swiecki, M.K.; Griguer, C.E.; Lisanby, M.W.; Bullard, D.C.; Turnbough, C.L.; Kearney, J.F. The integrin Mac-1 (CR3) mediates internalization and directs Bacillus anthracis spores into professional phagocytes. Proc. Natl. Acad. Sci. USA 2008, 105, 1261–1266, doi:10.1073/pnas.0709321105. 18216258
[11]
Hughes, M.A.; Green, C.S.; Lowchyj, L.; Lee, G.M.; Grippe, V.K.; Smith, M.F., Jr.; Huang, L.-Y.; Harvill, E.T.; Merkel, T.J. MyD88-dependent signaling contributes to protection following Bacillus anthracis spore challenge of mice: implications for Toll-like receptor signaling. Infect. Immun. 2005, 73, 7535–7540, doi:10.1128/IAI.73.11.7535-7540.2005. 16239556
[12]
Bozue, J.; Cote, C.K.; Moody, K.L.; Welkos, S.L. Fully virulent Bacillus anthracis does not require the immunodominant protein BclA for pathogenesis. Infect. Immun. 2007, 75, 508–511, doi:10.1128/IAI.01202-06. 17074844
[13]
Bozue, J.; Moody, K.L.; Cote, C.K.; Stiles, B.G.; Friedlander, A.M.; Welkos, S.L.; Hale, M.L. Bacillus anthracis Spores of the bclA Mutant Exhibit Increased Adherence to Epithelial Cells, Fibroblasts, and Endothelial Cells but Not to Macrophages. Infect. Immu.n 2007, 75, 4498–4505, doi:10.1128/IAI.00434-07.
[14]
Premanandan, C.; Storozuk, C.A.; Clay, C.D.; Lairmore, M.D.; Schlesinger, L.S.; Phipps, A.J. Complement protein C3 binding to Bacillus anthracis spores enhances phagocytosis by human macrophages. Microb. Pathog. 2009, 46, 306–314, doi:10.1016/j.micpath.2009.03.004.
[15]
Gu, C.; Jenkins, S.A.; Xue, Q.; Xu, Y. Activation of the Classical Complement Pathway by Bacillus anthracis Is the Primary Mechanism for Spore Phagocytosis and Involves the Spore Surface Protein BclA. J Immunol. 2012, 188, 4421–4431, doi:10.4049/jimmunol.1102092.
[16]
Chung, M.C.; Tonry, J.H.; Narayanan, A.; Manes, N.P.; Mackie, R.S.; Gutting, B.; Mukherjee, D.V.; Popova, T.G.; Kashanchi, F.; Bailey, C.L.; et al. Bacillus anthracis interacts with plasmin(ogen) to evade C3b-dependent innate immunity. PLoS One 2011, 6, e18119, doi:10.1371/journal.pone.0018119. 21464960
Alix, E.; Mukherjee, S.; Roy, C.R. Subversion of membrane transport pathways by vacuolar pathogens. J. Cell Biol. 2011, 195, 943–952, doi:10.1083/jcb.201105019. 22123831
[19]
Diacovich, L.; Gorvel, J.P. Bacterial manipulation of innate immunity to promote infection. Nat. Rev. Microbiol. 2010, 8, 117–128, doi:10.1038/nrmicro2295. 20075926
[20]
Blanchet, F.P.; Piguet, V. Immunoamphisomes in dendritic cells amplify TLR signaling and enhance exogenous antigen presentation on MHC-II. Autophagy 2010, 6, 816–818, doi:10.4161/auto.6.6.12623. 20595805
[21]
Sanjuan, M.A.; Milasta, S.; Green, D.R. Toll-like receptor signaling in the lysosomal pathways. Immunol. Rev. 2009, 227, 203–220, doi:10.1111/j.1600-065X.2008.00732.x. 19120486
[22]
Kumar, Y.; Valdivia, R.H. Leading a sheltered life: intracellular pathogens and maintenance of vacuolar compartments. Cell Host Microbe. 2009, 5, 593–601, doi:10.1016/j.chom.2009.05.014. 19527886
[23]
Guidi-Rontani, C.; Weber-Levy, M.; Labruyere, E.; Mock, M. Germination of Bacillus anthracis spores within alveolar macrophages. Mol. Microbiol. 1999, 31, 9–17, doi:10.1046/j.1365-2958.1999.01137.x.
[24]
Banks, D.J.; Barnajian, M.; Maldonado-Arocho, F.J.; Sanchez, A.M.; Bradley, K.A. Anthrax toxin receptor 2 mediates Bacillus anthracis killing of macrophages following spore challenge. Cell Microbiol. 2005, 7, 1173–1185, doi:10.1111/j.1462-5822.2005.00545.x. 16008584
[25]
Barry, A.O.; Mege, J.L.; Ghigo, E. Hijacked phagosomes and leukocyte activation: an intimate relationship. J. Leukoc. Biol. 2011, 89, 373–382, doi:10.1189/jlb.0510270. 20720162
[26]
Hu, H.; Sa, Q.; Koehler, T.M.; Aronson, A.I.; Zhou, D. Inactivation of Bacillus anthracis spores in murine primary macrophages. Cell Microbiol. 2006, 8, 1634–1642, doi:10.1111/j.1462-5822.2006.00738.x.
[27]
Welkos, S.; Friedlander, A.; Weeks, S.; Little, S.; Mendelson, I. In-vitro characterisation of the phagocytosis and fate of anthrax spores in macrophages and the effects of anti-PA antibody. J. Med. Microbiol. 2002, 51, 821–831. 12435060
Tonello, F.; Montecucco, C. The anthrax lethal factor and its MAPK kinase-specific metalloprotease activity. Mol. Aspects Med. 2009, 30, 431–438, doi:10.1016/j.mam.2009.07.006. 19665472
[32]
Moayeri, M.; Leppla, S.H. Cellular and systemic effects of anthrax lethal toxin and edema toxin. Mol. Aspects Med. 2009, 30, 439–455, doi:10.1016/j.mam.2009.07.003. 19638283
[33]
Yeager, L.A.; Chopra, A.K.; Peterson, J.W. Bacillus anthracis edema toxin suppresses human macrophage phagocytosis and cytoskeletal remodeling via the protein kinase A and exchange protein activated by cyclic AMP pathways. Infect. Immun. 2009, 77, 2530–2543, doi:10.1128/IAI.00905-08.
Terra, J.K.; Cote, C.K.; France, B.; Jenkins, A.L.; Bozue, J.A.; Welkos, S.L.; LeVine, S.M.; Bradley, K.A. Cutting edge: resistance to Bacillus anthracis infection mediated by a lethal toxin sensitive allele of Nalp1b/Nlrp1b. J. Immunol. 2010, 184, 17–20, doi:10.4049/jimmunol.0903114. 19949100
[38]
Moayeri, M.; Crown, D.; Newman, Z.L.; Okugawa, S.; Eckhaus, M.; Cataisson, C.; Liu, S.; Sastalla, I.; Leppla, S.H. Inflammasome sensor Nlrp1b-dependent resistance to anthrax is mediated by caspase-1, IL-1 signaling and neutrophil recruitment. PLoS Pathog. 2010, 6, e1001222, doi:10.1371/journal.ppat.1001222. 21170303
[39]
Hahn, B.L.; Bischof, T.S.; Sohnle, P.G. Superficial exudates of neutrophils prevent invasion of Bacillus anthracis bacilli into abraded skin of resistant mice. Int. J. Exp. Pathol. 2008, 89, 180–187, doi:10.1111/j.1365-2613.2008.00584.x. 18460070
[40]
Mayer-Scholl, A.; Hurwitz, R.; Brinkmann, V.; Schmid, M.; Jungblut, P.; Weinrauch, Y.; Zychlinsky, A. Human neutrophils kill Bacillus anthracis. PLoS Pathog. 2005, 1, e23, doi:10.1371/journal.ppat.0010023.
[41]
Terra, J.K.; France, B.; Cote, C.K.; Jenkins, A.; Bozue, J.A.; Welkos, S.L.; Bhargava, R.; Ho, C.L.; Mehrabian, M.; Pan, C.; et al. Allelic variation on murine chromosome 11 modifies host inflammatory responses and resistance to Bacillus anthracis. PLoS Pathog. 2011, 7, e1002469, doi:10.1371/journal.ppat.1002469.
[42]
Cote, C.K.; Rossi, C.A.; Kang, A.S.; Morrow, P.R.; Lee, J.S.; Welkos, S.L. The detection of protective antigen (PA) associated with spores of Bacillus anthracis and the effects of anti-PA antibodies on spore germination and macrophage interactions. Microb. Pathog. 2005, 38, 209–225, doi:10.1016/j.micpath.2005.02.001.
[43]
Scobie, H.M.; Rainey, G.J.; Bradley, K.A.; Young, J.A. Human capillary morphogenesis protein 2 functions as an anthrax toxin receptor. Proc. Natl. Acad. Sci. USA 2003, 100, 5170–5174, doi:10.1073/pnas.0431098100. 12700348
[44]
Reeves, C.V.; Dufraine, J.; Young, J.A.; Kitajewski, J. Anthrax toxin receptor 2 is expressed in murine and tumor vasculature and functions in endothelial proliferation and morphogenesis. Oncogene 2010, 29, 789–801, doi:10.1038/onc.2009.383. 19901963
[45]
Klimpel, K.R.; Molloy, S.S.; Thomas, G.; Leppla, S.H. Anthrax toxin protective antigen is activated by a cell surface protease with the sequence specificity and catalytic properties of furin. Proc. Natl. Acad. Sci. USA 1992, 89, 10277–10281, doi:10.1073/pnas.89.21.10277. 1438214
[46]
Panchal, R.G.; Halverson, K.M.; Ribot, W.; Lane, D.; Kenny, T.; Abshire, T.G.; Ezzell, J.W.; Hoover, T.A.; Powell, B.; Little, S.; et al. Purified Bacillus anthracis lethal toxin complex formed in vitro and during infection exhibits functional and biological activity. J. Biol. Chem. 2005, 280, 10834–10839, doi:10.1074/jbc.M412210200. 15644338
[47]
Molloy, S.S.; Anderson, E.D.; Jean, F.; Thomas, G. Bi-cycling the furin pathway: from TGN localization to pathogen activation and embryogenesis. Trends Cell Biol. 1999, 9, 28–35, doi:10.1016/S0962-8924(98)01382-8. 10087614
[48]
Komiyama, T.; Coppola, J.M.; Larsen, M.J.; van Dort, M.E.; Ross, B.D.; Day, R.; Rehemtulla, A.; Fuller, R.S. Inhibition of furin/proprotein convertase-catalyzed surface and intracellular processing by small molecules. J. Biol. Chem. 2009, 284, 15729–15738, doi:10.1074/jbc.M901540200. 19332539
[49]
Anes, E.; Peyron, P.; Staali, L.; Jordao, L.; Gutierrez, M.G.; Kress, H.; Hagedorn, M.; Maridonneau-Parini, I.; Skinner, M.A.; Wildeman, A.G.; et al. Dynamic life and death interactions between Mycobacterium smegmatis and J774 macrophages. Cell Microbiol. 2006, 8, 939–960, doi:10.1111/j.1462-5822.2005.00675.x.
[50]
Kalamidas, S.A.; Kuehnel, M.P.; Peyron, P.; Rybin, V.; Rauch, S.; Kotoulas, O.B.; Houslay, M.; Hemmings, B.A.; Gutierrez, M.G.; Anes, E.; et al. cAMP synthesis and degradation by phagosomes regulate actin assembly and fusion events: consequences for mycobacteria. J. Cell. Sci. 2006, 119, 3686–3694, doi:10.1242/jcs.03091. 16931599
[51]
Gimenez, A.P.; Wu, Y.-Z.; Paya, M.; Delclaux, C.; Touqui, L.; Goossens, P.L. High bactericidal efficiency of type iia phospholipase A2 against Bacillus anthracis and inhibition of its secretion by the lethal toxin. J. Immunol. 2004, 173, 521–530. 15210813
Steinberg, B.E.; Grinstein, S. Pathogen destruction versus intracellular survival: the role of lipids as phagosomal fate determinants. J. Clin. Invest. 2008, 118, 2002–2011, doi:10.1172/JCI35433. 18523652
[54]
Cote, C.K.; DiMezzo, T.L.; Banks, D.J.; France, B.; Bradley, K.A.; Welkos, S.L. Early interactions between fully virulent Bacillus anthracis and macrophages that influence the balance between spore clearance and development of a lethal infection. Microbes. Infect. 2008, 10, 613–619, doi:10.1016/j.micinf.2008.02.006.
[55]
Tan, Y.K.; Vu, H.A.; Kusuma, C.M.; Wu, A. Implications of autophagy in anthrax pathogenicity. Autophagy 2009, 5, 734–735, doi:10.4161/auto.5.5.8567. 19395870
[56]
Ebrahimi, C.M.; Sheen, T.R.; Renken, C.W.; Gottlieb, R.A.; Doran, K.S. Contribution of lethal toxin and edema toxin to the pathogenesis of anthrax meningitis. Infect. Immun. 2011, 79, 2510–2518, doi:10.1128/IAI.00006-11.
[57]
Shahnazari, S.; Namolovan, A.; Mogridge, J.; Kim, P.K.; Brumell, J.H. Bacterial toxins can inhibit host cell autophagy through cAMP generation. Autophagy 2011, 7, 957–965, doi:10.4161/auto.7.9.16435. 21606683
[58]
Tweten, R.K. Cholesterol-dependent cytolysins, a family of versatile pore-forming toxins. Infect. Immun. 2005, 73, 6199–6209, doi:10.1128/IAI.73.10.6199-6209.2005. 16177291
[59]
Shannon, J.G.; Ross, C.L.; Koehler, T.M.; Rest, R.F. Characterization of anthrolysin O, the Bacillus anthracis cholesterol-dependent cytolysin. Infect. Immun. 2003, 71, 3183–3189, doi:10.1128/IAI.71.6.3183-3189.2003.
[60]
Mosser, E.M.; Rest, R.F. The Bacillus anthracis cholesterol-dependent cytolysin, Anthrolysin O, kills human neutrophils, monocytes and macrophages. BMC Microbiol. 2006, 6, 56, doi:10.1186/1471-2180-6-56.
[61]
Cocklin, S.; Jost, M.; Robertson, N.M.; Weeks, S.D.; Weber, H.-W.; Young, E.; Seal, S.; Zhang, C.; Mosser, E.; Loll, P.J.; et al. Real-time monitoring of the membrane-binding and insertion properties of the cholesterol-dependent cytolysin anthrolysin O from Bacillus anthracis. J. Mol. Recognit. 2006, 19, 354–362, doi:10.1002/jmr.784.
[62]
Bourdeau, R.W.; Malito, E.; Chenal, A.; Bishop, B.L.; Musch, M.W.; Villereal, M.L.; Chang, E.B.; Mosser, E.M.; Rest, R.F.; Tang, W.J. Cellular functions and X-ray structure of anthrolysin O, a cholesterol-dependent cytolysin secreted by Bacillus anthracis. J. Biol. Chem. 2009, 284, 14645–14656, doi:10.1074/jbc.M807631200. 19307185
[63]
Bishop, B.L.; Lodolce, J.P.; Kolodziej, L.E.; Boone, D.L.; Tang, W.J. The role of anthrolysin O in gut epithelial barrier disruption during Bacillus anthracis infection. Biochem. Biophys. Res. Commun 2010, 394, 254–259, doi:10.1016/j.bbrc.2010.02.091.
Wei, Z.; Schnupf, P.; Poussin, M.A.; Zenewicz, L.A.; Shen, H.; Goldfine, H. Characterization of Listeria monocytogenes expressing anthrolysin O and phosphatidylinositol-specific phospholipase C from Bacillus anthracis. Infect. Immun. 2005, 73, 6639–6646, doi:10.1128/IAI.73.10.6639-6646.2005.
[68]
Heffernan, B.J.; Thomason, B.; Herring-Palmer, A.; Hanna, P. Bacillus anthracis anthrolysin O and three phospholipases C are functionally redundant in a murine model of inhalation anthrax. FEMS Microbiol. Lett. 2007, 271, 98–105, doi:10.1111/j.1574-6968.2007.00713.x.
[69]
Read, T.D.; Peterson, S.N.; Tourasse, N.; Baillie, L.W.; Paulsen, I.T.; Nelson, K.E.; Tettelin, H.; Fouts, D.E.; Eisen, J.A.; Gill, S.R.; et al. The genome sequence of Bacillus anthracis Ames and comparison to closely related bacteria. Nature 2003, 423, 81–86, doi:10.1038/nature01586. 12721629
[70]
Heffernan, B.J.; Thomason, B.; Herring-Palmer, A.; Shaughnessy, L.; McDonald, R.; Fisher, N.; Huffnagle, G.B.; Hanna, P. Bacillus anthracis phospholipases C facilitate macrophage-associated growth and contribute to virulence in a murine model of inhalation anthrax. Infect. Immun. 2006, 74, 3756–3764, doi:10.1128/IAI.00307-06. 16790747
[71]
Alberti-Segui, C.; Goeden, K.R.; Higgins, D.E. Differential function of Listeria monocytogenes listeriolysin O and phospholipases C in vacuolar dissolution following cell-to-cell spread. Cell Microbiol. 2007, 9, 179–195, doi:10.1111/j.1462-5822.2006.00780.x.
[72]
Raines, K.W.; Kang, T.J.; Hibbs, S.; Cao, G.-L.; Weaver, J.; Tsai, P.; Baillie, L.; Cross, A.S.; Rosen, G.M. Importance of nitric oxide synthase in the control of infection by Bacillus anthracis. Infect. Immun. 2006, 74, 2268–2276, doi:10.1128/IAI.74.4.2268-2276.2006. 16552057
[73]
Weaver, J.; Kang, T.J.; Raines, K.W.; Cao, G.L.; Hibbs, S.; Tsai, P.; Baillie, L.; Rosen, G.M.; Cross, A.S. Protective role of Bacillus anthracis exosporium in macrophage-mediated killing by nitric oxide. Infect. Immun. 2007, 75, 3894–3901, doi:10.1128/IAI.00283-07. 17502390
Viator, R.J.; Rest, R.F.; Hildebrandt, E.; McGee, D.J. Characterization of Bacillus anthracis arginase: effects of pH, temperature, and cell viability on metal preference. BMC Biochem. 2008, 9, 15, doi:10.1186/1471-2091-9-15.
[76]
Cybulski, R.J.; Sanz, P.; Alem, F.; Stibitz, S.; Bull, R.L.; O’Brien, A.D. Four superoxide dismutases contribute to Bacillus anthracis virulence and provide spores with redundant protection from oxidative stress. Infect. Immun. 2009, 77, 274–285, doi:10.1128/IAI.00515-08. 18955476
[77]
Zamocky, M.; Furtmüller, P.G.; Obinger, C. Evolution of catalases from bacteria to humans. Antioxid Redox Signal. 2008, 10, 1527–1548, doi:10.1089/ars.2008.2046. 18498226
[78]
Shatalin, K.; Gusarov, I.; Avetissova, E.; Shatalina, Y.; McQuade, L.E.; Lippard, S.J.; Nudler, E. Bacillus anthracis-derived nitric oxide is essential for pathogen virulence and survival in macrophages. Proc. Natl. Acad. Sci. USA 2008, 105, 1009–1013, doi:10.1073/pnas.0710950105. 18215992
[79]
Makino, S.; Watarai, M.; Cheun, H.I.; Shirahata, T.; Uchida, I. Effect of the lower molecular capsule released from the cell surface of Bacillus anthracis on the pathogenesis of anthrax. J. Infect. Dis. 2002, 186, 227–233, doi:10.1086/341299.
Ryter, A.; Frehel, C.; Rastogi, N.; David, H.L. Macrophage interaction with mycobacteria including M. leprae.. Acta Leprol. 1984, 2, 211–226. 6398582
[83]
Hart, P.D.; Young, M.R. Polyanionic agents inhibit phagosome-lysosome fusion in cultured macrophages: a reply to the suggestion of Goren, Vatter, and Fiscus to the contrary. J. Leukoc. Biol. 1988, 43, 179–182. 3422088
[84]
Yessine, M.A.; Leroux, J.C. Membrane-destabilizing polyanions: interaction with lipid bilayers and endosomal escape of biomacromolecules. Adv. Drug Deliv. Rev. 2004, 56, 999–1021, doi:10.1016/j.addr.2003.10.039. 15066757
[85]
Boyer, A.E.; Quinn, C.P.; Hoffmaster, A.R.; Kozel, T.R.; Saile, E.; Marston, C.K.; Percival, A.; Plikaytis, B.D.; Woolfitt, A.R.; Gallegos, M.; et al. Kinetics of lethal factor and poly-D-glutamic acid antigenemia during inhalation anthrax in rhesus macaques. Infect. Immun. 2009, 77, 3432–3441, doi:10.1128/IAI.00346-09. 19506008
[86]
Cote, C.K.; Rea, K.M.; Norris, S.L.; van Rooijen, N.; Welkos, S.L. The use of a model of in vivo macrophage depletion to study the role of macrophages during infection with Bacillus anthracis spores. Microb. Pathog. 2004, 37, 169–175, doi:10.1016/j.micpath.2004.06.013.
[87]
Kang, T.J.; Fenton, M.J.; Weiner, M.A.; Hibbs, S.; Basu, S.; Baillie, L.; Cross, A.S. Murine macrophages kill the vegetative form of Bacillus anthracis. Infect. Immun. 2005, 73, 7495–7501, doi:10.1128/IAI.73.11.7495-7501.2005.
[88]
Gut, I.M.; Tamilselvam, B.; Prouty, A.M.; Stojkovic, B.; Czeschin, S.; van der Donk, W.A.; Blanke, S.R. Bacillus anthracis spore interactions with mammalian cells: relationship between germination state and the outcome of in vitro. BMC Microbiol. 2011, 11, 46, doi:10.1186/1471-2180-11-46.
[89]
Cote, C.K.; Van Rooijen, N.; Welkos, S.L. Roles of macrophages and neutrophils in the early host response to Bacillus anthracis spores in a mouse model of infection. Infect. Immun. 2006, 74, 469–480, doi:10.1128/IAI.74.1.469-480.2006.
Shetron-Rama, L.M.; Herring-Palmer, A.C.; Huffnagle, G.B.; Hanna, P. Transport of Bacillus anthracis from the lungs to the draining lymph nodes is a rapid process facilitated by CD11c+ cells. Microb. Pathog. 2010, 49, 38–46, doi:10.1016/j.micpath.2010.02.004.
[92]
Savina, A.; Jancic, C.; Hugues, S.; Guermonprez, P.; Vargas, P.; Moura, I.C.; Lennon-Duménil, A.M.; Seabra, M.C.; Raposo, G.; Amigorena, S. NOX2 controls phagosomal pH to regulate antigen processing during crosspresentation by dendritic cells. Cell 2006, 126, 205–218, doi:10.1016/j.cell.2006.05.035. 16839887
[93]
Russell, D.G.; Vanderven, B.C.; Glennie, S.; Mwandumba, H.; Heyderman, R.S. The macrophage marches on its phagosome: dynamic assays of phagosome function. Nat. Rev. Immunol. 2009, 9, 594–600, doi:10.1038/nri2591. 19590530
[94]
Schwartz, M. Dr. Jekyll and Mr. Hyde: a short history of anthrax. Mol. Aspects Med. 2009, 30, 347–355, doi:10.1016/j.mam.2009.06.004.
