Article Review: Immune Response against Some Bacterial Toxins

Authors

  • Zainab Zamel Khalaf Department of Biology, College of Science, University of Baghdad, Baghdad, IRAQ.
  • Heba Khaleel Tawfeeq Department of Chemistry, College of Science, University of Baghdad, Baghdad, Iraq.

Keywords:

Shiga toxin, Cholera toxin, Pertussis toxin, Alpha toxin, Anthrax toxin, Botulinum toxin, Immune

Abstract

Bacterial toxins are considered to be virulence factors due to the fact that they interfere with the normal processes of the host cell in which they are found. The interplay between the infectious processes of bacteria and the immune system is what causes this impact. In this discussion, we are going to focus on bacterial toxins that act in the extracellular environment, especially on those that impair the activity of macrophages and neutrophils. These toxins are of particular interest since they may be found in a wide variety of bacteria. We will be concentrating our efforts, in particular, on the toxins that are generated by Gram-positive and Gram-negative bacteria. These toxins are able to interact with and have an effect on the many different types of immune cells. We utilize the Shiga toxin, cholera toxin (CT), and pertussis toxin as examples of Gram-negative toxins (PT). As examples of Gram Positive toxins, we use Alpha toxin, anthrax toxin, and botulinum toxin (BONT). In total, we look at six different types of bacterial toxins. According to the findings of the study, Shiga toxins, which are associated with the production of cytokines, chemokines, and macrophages, might thus result in post-translational modification. The cholera toxin induced a mucosal response that was mediated by secretory IgA, whereas the pertussis toxin inhibited the migration of macrophages and interacted with phagocytosis. The process by which cells take in and digest foreign material is called phagocytosis. It was revealed that S. aureus bacteremia led to an increase in the number of Th17 cells, while at the same time alpha-toxin led to a decrease in the number of Th1 cells. The anthrax toxin inhibits the synthesis of cytokines and chemokines, both of which are involved in the inflammatory response. This, in turn, causes the death of macrophages by necrosis and apoptosis. When being treated with BoNT, it was found that cells produced elevated amounts of TNF and NO in a dose-dependent way. This was determined after the cells were exposed to BoNT. This was the conclusion reached.

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References

Wynn T. A., Chawla A., Pollard J. W. (2013). Macrophage biology in development, homeostasis and disease. Nature 496 445–455. 10.1038/nature12034.

Silva M. T. (2010). When two is better than one: macrophages and neutrophils work in concert in innate immunity as complementary and cooperative partners of a myeloid phagocyte system. J. Leukoc. Biol. 87 93–106.

Silva M. T., Correia-Neves M. (2012). Neutrophils and macrophages: the main partners of phagocyte cell systems. Front. Immunol. 3:174

Lemichez E., Barbieri J. T. (2013). General aspects and recent advances on bacterial protein toxins. Cold Spring Harb Perspect. Med. 3:a013573 10.1101

Pittman M. (1984). The concept of pertussis as a toxin-mediated disease. Pediatr. Infect. Dis. 3 467–486. 10.1097

Carbonetti N. H. (2007). Immunomodulation in the pathogenesis of Bordetella pertussis infection and disease. Curr. Opin. Pharmacol. 7 272–278.

Johnson, A. G., S. Gaines, and M. Landy. 1956. Studies on the O antigen of Salmonella typhosa. V. Enhancement of antibody response to protein antigens by the purified lipopolysaccharide. J. Exp. Med. 103:225–246.

Lycke, N., and J. Holmgren. 1986. Strong adjuvant properties of cholera toxin on gut mucosal immune responses to orally presented antigens. Immunology 59:301–308.

Moo-Seung Lee and Vernon L. Tesh. (2019). Roles of Shiga Toxins in Immunopathology. Toxins, 11, 212; toxins11040212.

Bonifacius A, Goldmann O, Floess S, Holtfreter S, Robert PA, Nordengrün M, Kruse F, Lochner M, Falk CS, Schmitz I, Bröker BM, Medina E and Huehn J (2020) Staphylococcus aureus Alpha-Toxin Limits Type 1 While Fostering Type 3 Immune Responses. Front. Immunol. 11:1579. doi: 10.3389/fimmu.2020.01579

Barth H., Fischer S., Moglich A., Fortsch C. (2015). Clostridial C3 toxins target monocytes/macrophages and modulate their functions. Front. Immunol. 6:339

Strockbine, N.A.; Jackson, M.P.; Sung, L.M.; Holmes, R.K.; O'Brien, A.D. Cloning and sequencing of the genes for Shiga toxin from Shigella dysenteriae type 1. J. Bacteriol. 1988, 170, 1116–1122.

Imamovic, L.; Jofre, J.; Schmidt, H.; Serra-Moreno, R.; Muniesa, M. Phage-mediated Shiga toxin 2 gene transfer in food and water. Appl. Environ. Microbiol. 2009, 75, 1764–1768.

Johnson KE, Thorpe CM, Sears CL: The emerging clinical importance of non-O157 Shiga toxin-producing Escherichia coli. Clin Infect Dis 2006, 43(12):1587–1595.

Bettelheim KA: Non-O157 Shiga-toxin-producing Escherichia coli. Lancet Infect Dis 2012, 12(1):12.

O’Brien AD, Tesh VL, Donohue-Rolfe A, Jackson MP, Olsnes S, Sandvig K, Lindberg AA, Keusch GT: Shiga toxin: biochemistry, genetics, mode of action, androle in pathogenesis. Curr Top Microbiol Immunol 1992, 180:65–94.

Karmali MA, Mascarenhas M, Petric M, Dutil L, Rahn K, Ludwig K, Arbus GS, Michel P, Sherman PM, Wilson J, Johnson R, Kaper JB: Age-specific frequencies of antibodies to Escherichia coli verocytotoxins (Shiga toxins) 1 and 2 among urban and rural populations in southern Ontario. J Infect Dis 2003, 188(11):1724–1729.

Karmali MA, Petric M, Winkler M, Bielaszewska M, Brunton J, van de Kar N, Morooka T, Nair GB, Richardson SE, Arbus GS: Enzyme-linked immunosorbent assay for detection of immunoglobulin G antibodies to Escherichia coli Vero cytotoxin 1. J Clin Microbiol 1994, 32(6):1457–1463.

Tesh, V.L. The induction of apoptosis by Shiga toxins and ricin. Curr. Top. Microbiol. Immunol. 2012, 357, 137–178.

Barrett TJ, Green JH, Griffin PM, Pavia AT, Ostroff SM, Wachsmuth LK: Enzyme linked immunosorbent assays for detecting antibodies to Shiga-like toxin I, Shiga-like toxin II, and Escherichia coli O157:H7 lipopolysaccharide in human serum. Curr Microbiol 1991, 23:189–195.

Tesh, V.L.; Ramegowda, B.; Samuel, J.E. Purified Shiga-like toxins induce expression of proinflammatory cytokines from murine peritoneal macrophages. Infect. Immun. 1994, 62, 5085–5094.

Leyva-Illades, D.; Cherla, R.P.; Lee, M.S.; Tesh, V.L. Regulation of cytokine and chemokine expression by the ribotoxic stress response elicited by Shiga toxin type 1 in human macrophage-like THP-1 cells. Infect. Immun. 2012, 80, 2109–2120.

Legros, N.; Pohlentz, G.; Steil, D.; Müthing, J. Shiga toxin-glycosphingolipid interaction: Status quo of research with focus on primary human brain and kidney endothelial cells. Int. J. Med. Microbiol. 2018, 308, 1073–1084.

Keepers, T.R.; Gross, L.K.; Obrig, T.G. Monocyte chemoattractant protein 1, macrophage inflammatory protein 1_, and RANTES recruit macrophages to the kidney in a mouse model of hemolytic-uremic syndrone. Infect. Immun. 2007, 75, 1229–1236.

Wadolkowski, E.A.; Sung, L.M.; Burris, J.A.; Samuel, J.E.; O’Brien, A.D. Acute renal tubular necrosis and death of mice orally infected with Escherichia coli strains that produce Shiga-like toxin type II. Infect. Immun. 1990, 58, 3959–3965.

Porubsky, S.; Federico, G.; Müthing, J.; Jennemann, R.; Gretz, N.; Büttner, S.; Obermüller, N.; Jung, O.; Hauser, I.A.; Gröne, E.; et al. Direct acute tubular damage contributes to Shigatoxin-mediated kidney failure. J. Pathol. 2014, 234, 120–133.

Lee, M.S.; Kwon, H.; Lee, E.Y.; Kim, D.J.; Park, J.H.; Tesh, V.L.; Oh, T.K.; Kim, M.H. Shiga toxins activate the NLRP3 inflammasome pathway to promote both production of the proinflammatory cytokine interleukin-1beta and apoptotic cell death. Infect. Immun. 2016, 84, 172–186.

Spangler B D. Structure and function of cholera toxin and the Escherichia coli heat-labile enterotoxin. Microbiol Rev. 1992;56:622–647

Svenner holm AM, Gothefors L, Sack DA, Bardhan PK, Holmgren J. Local and systemic antibody responses and immunological memory in humans after immunization with cholera B subunit by different routes. Bull World Health Organ 1984; 62:909 –18.

Snider, D. P. 1995. The mucosal adjuvant activities of ADP-ribosylating bacterial enterotoxins. Crit. Rev. Immunol. 15:317–348.

Marinaro M, Staats H F, Hiroi T, Jackson R J, Coste M, Boyaka P N, Okahashi N, Yamamoto M, Kiyono H, Bluethmann H, Fujihashi K, McGhee J R. Mucosal adjuvant effect of cholera toxin in mice results from induction of T helper 2 (Th2) cells and IL-4. J Immunol. 1995;155:4621–4629.

Simecka, J. W., Jackson, R. J., Kiyono, H., McGhee, J. R. (2000) Mucosally induced immunoglobulin E-associated inflammation in the respiratory tract. Infect. Immun. 68, 672–679.

Richards, C. M., Shimeld, C., Williams, N. A., Hill, T. J. (1998) Induction of mucosal immunity against herpes simplex virus type 1 in the mouse protects against ocular infection and establishment of latency. J. Infect. Dis. 177, 1451–1457.

Stein,P.E.,Boodhoo,A.,Armstrong,G.D.,Heerze,L.D.,Cockle,S.A.,Klein, M. H.,etal.(1994). Structure of a pertussis toxin-sugar complex as a model for receptor binding. Nat.Struct.Biol. 1, 591–596.doi:10.1038/nsb0994-591.

Meade,B.D.,Kind,P.D.,Ewell,J.B.,McGrath,P.P.,andManclark,C.R.(1984). In vitro inhibition of murine macrophage emigration by Bordetella pertussis lymphocytosis-promoting factor. Infect. Immun. 45, 718–725.

Mork, T.,andHancock,R.E.(1993).Mechanisms of non opsonicphagocytosis of Pseudomonas aeruginosa. Infect. Immun. 61, 3287–3293.

Andreasen, C.,and Carbonetti,N.H.(2008). Pertussis toxin inhibits early chemokine production to delay neutrophil recruitment in response to Bordetella pertussis respiratoryt ract infection in mice. Infect. Immun. 76, 5139–5148.doi:10.1128/IAI.00895-08.

Andreasen, C., and Carbonetti,N.H.(2009). Role of neutrophils in response to Bordetella pertussis infection in mice. Infect. Immun. 77, 1182–1188.doi: 10.1128/IAI.01150-08

Andreasen,C.,Powell,D.A.,andCarbonetti,N.H.(2009).Pertussis toxin stimulates IL-17production in response to Bordetella pertussis infection in mice. PLoSONE 4:e7079.doi:10.1371.

Lowy FD. Staphylococcus aureus infections. N Engl J Med. (1998) 339:520–32. doi: 10.1056/NEJM199808203390806

Wertheim HF, Melles DC, Vos MC, Van Leeuwen W, Van Belkum A, Verbrugh HA, et al. The role of nasal carriage in Staphylococcus aureus infections. Lancet Infect Dis. (2005) 5:751–62. doi: 10.1016/S1473-3099(05)70295-4

Baker S, Thomson N, Weill FX, Holt KE. Genomic insights into the emergence and spread of antimicrobial-resistant bacterial pathogens. Science. (2018) 360:733–8. doi: 10.1126/science.aar3777

Cassini A, Högberg LD, Plachouras D, Quattrocchi A, Hoxha A, Simonsen GS, et al. Attributable deaths and disability-adjusted life-years caused by infections with antibiotic-resistant bacteria in the EU and the European Economic Area in 2015: a population-level modelling analysis. Lancet Infect Dis. (2018) 19:56–66. doi: 10.1016/S1473-3099(18) 30605-4

Lakhundi S, Zhang K. Methicillin-resistant Staphylococcus aureus: molecular characterization, evolution, and epidemiology. Clin Microbiol Rev. (2018) 31: e00020-18. doi: 10.1128/CMR.00020-18

Calvano SE, Quimby FW, Antonacci AC, Reiser RF, Bergdoll MS, Dineen P. Analysis of the mitogenic effects of toxic shock toxin on human peripheral blood mononuclear cells in vitro. Clin Immunol Immunopathol. (1984) 33:99– 110. doi: 10.1016/0090-1229(84)90296-4

Glenny AT, Stevens MF. Staphylococcus toxins and antitoxins. J Pathol Bacteriol. (1935) 40:201–10. doi: 10.1002/path.1700400202

Berube BJ, Bubeck Wardenburg J. Staphylococcus aureus alpha-toxin: nearly a century of intrigue. Toxins. (2013) 5:1140–66. doi: 10.3390/toxins5061140

Berube BJ, BubeckWardenburg J. Staphylococcus aureus alpha-toxin: nearly a century of intrigue. Toxins. (2013) 5:1140–66. doi: 10.3390/toxins5061140

Wilke GA, BubeckWardenburg J. Role of a disintegrin and metalloprotease 10 in Staphylococcus aureus alpha-hemolysin-mediated cellular injury. Proc Natl Acad Sci USA. (2010) 107:13473–8. doi: 10.1073/pnas.1001815107

Kobayashi SD, Malachowa N, Whitney AR, Braughton KR, Gardner DJ, et al. (2011) Comparative analysis of USA300 virulence determinants in a rabbit model of skin and soft tissue infection. J Infect Dis 204: 937–941.

Kennedy AD, Bubeck Wardenburg J, Gardner DJ, Long D, Whitney AR, et al. (2010) Targeting of alpha-hemolysin by active or passive immunization decreases severity of USA300 skin infection in a mouse model. J Infect Dis 202: 1050–1058.

Kernodle DS, Voladri RK, Menzies BE, Hager CC, Edwards KM (1997) Expression of an antisense hla fragment in staphylococcus aureus reduces alphatoxin production in vitro and attenuates lethal activity in a murine model. Infect Immun 65: 179–184.

Bubeck Wardenburg J, Schneewind O (2008) Vaccine protection against staphylococcus aureus pneumonia. J Exp Med 205: 287–294.

Miller LS, Cho JS (2011) Immunity against staphylococcus aureus cutaneous infections. Nat Rev Immunol 11: 505–518.

Molne L, Verdrengh M, Tarkowski A (2000) Role of neutrophil leukocytes in cutaneous infection caused by staphylococcus aureus. Infect Immun 68: 6162–6167.

Molne L, Corthay A, Holmdahl R, Tarkowski A (2003) Role of gamma/delta T cell receptor-expressing lymphocytes in cutaneous infection caused by staphylococcus aureus. Clin Exp Immunol 132: 209–215.

Singh Y, Klimpel KR, Goel S, Swain PK, Leppla SH. Oligomerization of anthrax toxin protective antigen and binding of lethal factor during endocytic uptake into mammalian cells. Infect Immun1999; 67:1853–9.

Singh, Y., S. H. Leppla, R. Bhatnagar, and A. M. Friedlander. 1989. Internalization and processing of Bacillus anthracis lethal toxin by toxin-sensitive and -resistant cells. J. Biol. Chem. 264:11099–11102.

Marinaro, M., Staats, H. F., Hiroi, T., Jackson, R. J., Coste, M., Boyaka, P. N., Okahashi, N., Yamamoto, M., Kiyono, H., Bluethmann, H., et al. (1995) Mucosal adjuvant effect of cholera toxin in mice results from induction of T helper 2 (Th2) cells and IL-4. J. Immunol. 155, 4621– 4629

Taysse L, Daulon S, Calvet J, Delamanche S, Hilaire D, Bellier B, et al. Induction of acute lung injury after intranasal administration of toxin botulinum a complex. Toxicol Pathol. 2005; 33: 336–42

Pitt, M. L., S. Little, B. E. Ivins, P. Fellows, J. Boles, J. Barth, J. Hewetson, and A. M. Friedlander. 1999. In vitro correlate of immunity in an animal model of inhalational anthrax. J. Appl. Microbiol. 87:304.

Hatheway CL, Toxigenic clostridia. Clinical Microbiology Reviews 1990; 3: 66–98.

Schiavo GG, Benfenati F, Poulain B, Rossetto O, de Laureto PP, Tetanus and botulinum-B neurotoxins block neurotransmitter release by proteolytic cleavage of synaptobrevin. Nature 1992; 359: 832–835.

Benecke, R.(2012). Clinical Relevance of Botulinum Toxin Immunogenicity. Biodrugs 2012; 26 (2): e1-e9

Kim YJ, Kim J-H, Lee K-J, Choi M-M, Kim YH, Rhie G-e, et al. (2015) Botulinum Neurotoxin Type A Induces TLR2-Mediated Inflammatory Responses in Macrophages. PLoS ONE 10(4): e0120840.

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Published

2022-06-22

How to Cite

Zainab Zamel Khalaf, & Heba Khaleel Tawfeeq. (2022). Article Review: Immune Response against Some Bacterial Toxins. International Journal for Research in Applied Sciences and Biotechnology, 9(3), 262–267. Retrieved from https://www.ijrasb.com/index.php/ijrasb/article/view/419

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