REFERENCES
1. Housman G, Byler S, Heerboth S, Lapinska K, Longacre M, et al. Drug resistance in cancer: an overview. Cancers (Basel) 2014;6:1769-92.
3. Mansoori B, Mohammadi A, Davudian S, Shirjang S, Baradaran B. The different mechanisms of cancer drug resistance: a brief review. Adv Pharm Bull 2017;7:339-48.
4. Dagogo-Jack I, Shaw AT. Tumour heterogeneity and resistance to cancer therapies. Nat Rev Clin Oncol 2018;15:81-94.
5. Negrini S, Gorgoulis VG, Halazonetis TD. Genomic instability--an evolving hallmark of cancer. Nat Rev Mol Cell Biol 2010;11:220-8.
6. Chatterjee N, Bivona TG. Polytherapy and targeted cancer drug resistance. Trends Cancer 2019;5:170-82.
7. Pathania S, Bhatia R, Baldi A, Singh R, Rawal RK. Drug metabolizing enzymes and their inhibitors’ role in cancer resistance. Biomed Pharmacother 2018;105:53-65.
8. Calin GA, Trapasso F, Shimizu M, Dumitru CD, Yendamuri S, et al. Familial cancer associated with a polymorphism in ARLTS1. N Engl J Med 2005;352:1667-76.
10. Qu Y, Dou B, Tan H, Feng Y, Wang N, et al. Tumor microenvironment-driven non-cell-autonomous resistance to antineoplastic treatment. Mol Cancer 2019;18:69.
11. Elinav E, Nowarski R, Thaiss CA, Hu B, Jin C, et al. Inflammation-induced cancer: crosstalk between tumours, immune cells and microorganisms. Nat Rev Cancer 2013;13:759-71.
12. Fiedler E, Hemann MT. Aiding and abetting: how the tumor microenvironment protects cancer from chemotherapy. Ann Rev Cancer Biol 2019;3:409-28.
13. Sharma P, Hu-Lieskovan S, Wargo JA, Ribas A. Primary, adaptive, and acquired resistance to cancer immunotherapy. Cell 2017;168:707-23.
14. Snyder A, Makarov V, Merghoub T, Yuan J, Zaretsky JM, et al. Genetic basis for clinical response to CTLA-4 blockade in melanoma. N Engl J Med 2014;371:2189-99.
15. Rizvi NA, Hellmann MD, Snyder A, Kvistborg P, Makarov V, et al. Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science 2015;348:124-8.
16. Zaretsky JM, Garcia-Diaz A, Shin DS, Escuin-Ordinas H, Hugo W, et al. Mutations associated with acquired resistance to PD-1 blockade in melanoma. N Engl J Med 2016;375:819-29.
17. Saleh R, Elkord E. Acquired resistance to cancer immunotherapy: role of tumor-mediated immunosuppression. Semin Cancer Biol 2019. S1044-579X(19)30171-3
18. Panebianco C, Andriulli A, Pazienza V. Pharmacomicrobiomics: exploiting the drug-microbiota interactions in anticancer therapies. Microbiome 2018;6:92.
19. Alexander JL, Wilson ID, Teare J, Marchesi JR, Nicholson JK, et al. Gut microbiota modulation of chemotherapy efficacy and toxicity. Nat Rev Gastroenterol Hepatol 2017;14:356-65.
20. Fessler J, Matson V, Gajewski TF. Exploring the emerging role of the microbiome in cancer immunotherapy. J Immunother Cancer 2019;7:108.
21. Li H, He J, Jia W. The influence of gut microbiota on drug metabolism and toxicity. Expert Opin Drug Metab Toxicol 2016;12:31-40.
22. Ley RE, Peterson DA, Gordon JI. Ecological and evolutionary forces shaping microbial diversity in the human intestine. Cell 2006;124:837-48.
23. Lepage P, Leclerc MC, Joossens M, Mondot S, Blottière HM, et al. A metagenomic insight into our gut’s microbiome. Gut 2013;62:146-58.
24. Sender R, Fuchs S, Milo R. Are we really vastly outnumbered? Revisiting the ratio of bacterial to host cells in humans. Cell 2016;164:337-40.
25. Vernocchi P, Del Chierico F, Putignani L. Gut microbiota profiling: metabolomics based approach to unravel compounds affecting human health. Front Microbiol 2016;7:1144.
26. Levy M, Thaiss CA, Elinav E. Metabolites: messengers between the microbiota and the immune system. Genes Dev 2016;30:1589-97.
27. Medzhitov R. Toll-like receptors and innate immunity. Nat Rev Immunol 2001;1:135-45.
29. van Niel G, D’Angelo G, Raposo G. Shedding light on the cell biology of extracellular vesicles. Nat Rev Mol Cell Biol 2018;19:213-28.
30. Colombo M, Raposo G, Thery C. Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles. Annu Rev Cell Dev Biol 2014;30:255-89.
31. Deatherage BL, Cookson BT. Membrane vesicle release in bacteria, eukaryotes, and archaea: a conserved yet underappreciated aspect of microbial life. Infect Immun 2012;80:1948-57.
32. Peres da Silva R, Puccia R, Rodrigues ML, Oliveira DL, Joffe LS, et al. Extracellular vesicle-mediated export of fungal RNA. Sci Rep 2015;5:7763.
33. Choi DH, Kwon YM, Chiura HX, Yang EC, Bae SS, et al. Extracellular Vesicles of the Hyperthermophilic archaeon “thermococcus onnurineus” NA1T. Appl Environ Microbiol 2015;81:4591-9.
34. Tsatsaronis JA, Franch-Arroyo S, Resch U, Charpentier E. Extracellular vesicle RNA: a universal mediator of microbial communication? Trends Microbiol 2018;26:401-10.
35. Lee J, Lee EY, Kim SH, Kim DK, Park KS, et al. Staphylococcus aureus extracellular vesicles carry biologically active β-lactamase. Antimicrob Agents Chemother 2013;57:2589-95.
36. Ciofu O, Beveridge TJ, Kadurugamuwa J, Walther-Rasmussen J, Høiby N. Chromosomal beta-lactamase is packaged into membrane vesicles and secreted from Pseudomonas aeruginosa. J Antimicrob Chemother 2000;45:9-13.
37. Rumbo C, Fernández-Moreira E, Merino M, Poza M, Mendez JA, et al. Horizontal transfer of the OXA-24 carbapenemase gene via outer membrane vesicles: a new mechanism of dissemination of carbapenem resistance genes in Acinetobacter baumannii. Antimicrob Agents Chemother 2011;55:3084-90.
38. Medvedeva ES, Baranova NB, Mouzykantov AA, Grigorieva TY, Davydova MN, et al. Adaptation of mycoplasmas to antimicrobial agents: Acholeplasma laidlawii extracellular vesicles mediate the export of ciprofloxacin and a mutant gene related to the antibiotic target. Sci World J 2014;2014:150615.
39. Yaron S, Kolling GL, Simon L, Matthews KR. Vesicle-mediated transfer of virulence genes from Escherichia coli O157:H7 to other enteric bacteria. Appl Environ Microbiol 2000;66:4414-20.
40. Bitto NJ, Chapman R, Pidot S, Costin A, Lo C, et al. Bacterial membrane vesicles transport their DNA cargo into host cells. Sci Rep 2017;7:7072.
41. Lambertz U, Oviedo Ovando ME, Vasconcelos EJ, Unrau PJ, Myler PJ, et al. Small RNAs derived from tRNAs and rRNAs are highly enriched in exosomes from both old and new world Leishmania providing evidence for conserved exosomal RNA Packaging. BMC Genomics 2015;16:151.
42. Blenkiron C, Simonov D, Muthukaruppan A, Tsai P, Dauros P, et al. Uropathogenic escherichia coli releases extracellular vesicles that are associated with RNA. PLoS One 2016;11:e0160440.
43. Sjöström AE, Sandblad L, Uhlin BE, Wai SN. Membrane vesicle-mediated release of bacterial RNA. Sci Rep 2015;5:15329.
44. Beatty M, Guduric-Fuchs J, Brown E, Bridgett S, Chakravarthy U, et al. Small RNAs from plants, bacteria and fungi within the order Hypocreales are ubiquitous in human plasma. BMC Genomics 2014;15:933.
45. Wang K, Li H, Yuan Y, Etheridge A, Zhou Y, et al. The complex exogenous RNA spectra in human plasma: an interface with human gut biota? PLoS One 2012;7:e51009.
46. Stentz R, Carvalho AL, Jones EJ, Carding SR. Fantastic voyage: the journey of intestinal microbiota-derived microvesicles through the body. Biochem Soc Trans 2018;46:1021-7.
47. Choi JW, Um JH, Cho JH, Lee HJ. Tiny RNAs and their voyage via extracellular vesicles: Secretion of bacterial small RNA and eukaryotic microRNA. Exp Biol Med (Maywood) 2017;242:1475-81.
48. Ho MH, Chen CH, Goodwin JS, Wang BY, Xie H. Functional Advantages of Porphyromonas gingivalis Vesicles. PLoS One 2015;10:e0123448.
49. Kunsmann L, Rüter C, Bauwens A, Greune L, Glüder M, et al. Virulence from vesicles: Novel mechanisms of host cell injury by Escherichia coli O104:H4 outbreak strain. Sci Rep 2015;5:13252.
50. Thay B, Damm A, Kufer TA, Wai SN, Oscarsson J. Aggregatibacter actinomycetemcomitans outer membrane vesicles are internalized in human host cells and trigger NOD1- and NOD2-dependent NF-kappaB activation. Infect Immun 2014;82:4034-46.
51. Koeppen K, Hampton TH, Jarek M, Scharfe M, Gerber SA, et al. A novel mechanism of host-pathogen interaction through sRNA in bacterial outer membrane vesicles. PLoS Pathog 2016;12:e1005672.
52. Choi JW, Kim SC, Hong SH, Lee HJ. Secretable small RNAs via outer membrane vesicles in periodontal pathogens. J Dent Res 2017;96:458-66.
53. Kim MR, Hong SW, Choi EB, Lee WH, Kim YS, et al. Staphylococcus aureus-derived extracellular vesicles induce neutrophilic pulmonary inflammation via both Th1 and Th17 cell responses. Allergy 2012;67:1271-81.
54. Gottesman S. Micros for microbes: non-coding regulatory RNAs in bacteria. Trends Genet 2005;21:399-404.
55. Kang SM, Choi JW, Lee Y, Hong SH, Lee HJ. Identification of microRNA-size, small RNAs in Escherichia coli. Curr Microbiol 2013;67:609-13.
56. Lee HJ, Hong SH. Analysis of microRNA-size, small RNAs in Streptococcus mutans by deep sequencing. FEMS Microbiol Lett 2012;326:131-6.
57. Choi JW, Kwon TY, Hong SH, Lee HJ. Isolation and characterization of a microRNA-size secretable small RNA in streptococcus sanguinis. Cell Biochem Biophys 2018;76:293-301.
58. Han L, Lam EW, Sun Y. Extracellular vesicles in the tumor microenvironment: old stories, but new tales. Mol Cancer 2019;18:59.
59. Nauts HC, Swift WE, Coley BL. The treatment of malignant tumors by bacterial toxins as developed by the late William B. Coley, M.D., reviewed in the light of modern research. Cancer Res 1946;6:205-16.
60. Zbar B, Bernstein I, Tanaka T, Rapp HJ. Tumor immunity produced by the intradermal inoculation of living tumor cells and living Mycobacterium bovis (strain BCG). Science 1970;170:1217-8.
61. Aso Y, Akazan H. Prophylactic effect of a Lactobacillus casei preparation on the recurrence of superficial bladder cancer. BLP Study Group. Urol Int 1992;49:125-9.
62. Iida N, Dzutsev A, Stewart CA, Smith L, Bouladoux N, et al. Commensal bacteria control cancer response to therapy by modulating the tumor microenvironment. Science 2013;342:967-70.
63. Vétizou M, Pitt JM, Daillère R, Lepage P, Waldschmitt N, et al. Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Science 2015;350:1079-84.
64. Prieto PA, Yang JC, Sherry RM, Hughes MS, Kammula US, et al. CTLA-4 blockade with ipilimumab: long-term follow-up of 177 patients with metastatic melanoma. Clin Cancer Res 2012;18:2039-47.
65. Sivan A, Corrales L, Hubert N, Williams JB, Aquino-Michaels K, et al. Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy. Science 2015;350:1084-9.
66. Routy B, Le Chatelier E, Derosa L, Duong CPM, Alou MT, et al. Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors. Science 2018;359:91-7.
67. Collado MC, Derrien M, Isolauri E, de Vos WM, Salminen S. Intestinal integrity and Akkermansia muciniphila, a mucin-degrading member of the intestinal microbiota present in infants, adults, and the elderly. Appl Environ Microbiol 2007;73:7767-70.
68. Matson V, Fessler J, Bao R, Chongsuwat T, Zha Y, et al. The commensal microbiome is associated with anti-PD-1 efficacy in metastatic melanoma patients. Science 2018;359:104-8.
69. Gopalakrishnan V, Spencer CN, Nezi L, Reuben A, Andrews MC, et al. Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients. Science 2018;359:97-103.
70. Faith JJ, Ahern PP, Ridaura VK, Cheng J, Gordon JI. Identifying gut microbe-host phenotype relationships using combinatorial communities in gnotobiotic mice. Sci Transl Med 2014;6:220ra11.
72. Franchi L, Warner N, Viani K, Nuñez G. Function of Nod-like receptors in microbial recognition and host defense. Immunol Rev 2009;227:106-28.
73. Paulos CM, Wrzesinski C, Kaiser A, Hinrichs CS, Chieppa M, et al. Microbial translocation augments the function of adoptively transferred self/tumor-specific CD8+ T cells via TLR4 signaling. J Clin Invest 2007;117:2197-204.
74. Sun J, Shi YH, Le GW, Ma XY. Distinct immune response induced by peptidoglycan derived from Lactobacillus sp. World J Gastroenterol 2005;11:6330-7.
75. Hajam IA, Dar PA, Shahnawaz I, Jaume JC, Lee JH. Bacterial flagellin-a potent immunomodulatory agent. Exp Mol Med 2017;49:e373.
76. Leleux JA, Pradhan P, Roy K. Biophysical attributes of CpG presentation control TLR9 signaling to differentially polarize systemic immune responses. Cell Rep 2017;18:700-10.
77. Hall JA, Bouladoux N, Sun CM, Wohlfert EA, Blank RB, et al. Commensal DNA limits regulatory T cell conversion and is a natural adjuvant of intestinal immune responses. Immunity 2008;29:637-49.
78. Round JL, Mazmanian SK. Inducible Foxp3+ regulatory T-cell development by a commensal bacterium of the intestinal microbiota. Proc Natl Acad Sci U S A 2010;107:12204-9.
79. Rooks MG, Garrett WS. Gut microbiota, metabolites and host immunity. Nat Rev Immunol 2016;16:341-52.
81. Smith PM, Howitt MR, Panikov N, Michaud M, Gallini CA, et al. The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science 2013;341:569-73.
82. Arpaia N, Campbell C, Fan X, Dikiy S, van der Veeken J, et al. Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation. Nature 2013;504:451-5.
83. Park J, Kim M, Kang SG, Jannasch AH, Cooper B, et al. Short-chain fatty acids induce both effector and regulatory T cells by suppression of histone deacetylases and regulation of the mTOR-S6K pathway. Mucosal Immunol 2015;8:80-93.
84. Furusawa Y, Obata Y, Fukuda S, Endo TA, Nakato G, et al. Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature 2013;504:446-50.
85. Berman D, Parker SM, Siegel J, Chasalow SD, Weber J, et al. Blockade of cytotoxic T-lymphocyte antigen-4 by ipilimumab results in dysregulation of gastrointestinal immunity in patients with advanced melanoma. Cancer Immun 2010;10:11.
86. Denning TL, Kim G, Kronenberg M. Cutting edge: CD4+CD25+ regulatory T cells impaired for intestinal homing can prevent colitis. J Immunol 2005;174:7487-91.
87. Dubin K, Callahan MK, Ren B, Khanin R, Viale A, et al. Intestinal microbiome analyses identify melanoma patients at risk for checkpoint-blockade-induced colitis. Nat Commun 2016;7:10391.
88. Raymond E, Faivre S, Woynarowski JM, Chaney SG. Oxaliplatin: mechanism of action and antineoplastic activity. Semin Oncol 1998;25:4-12.
89. Siddik ZH. Cisplatin: mode of cytotoxic action and molecular basis of resistance. Oncogene 2003;22:7265-79.
90. Emadi A, Jones RJ, Brodsky RA. Cyclophosphamide and cancer: golden anniversary. Nat Rev Clin Oncol 2009;6:638-47.
91. Strauss G, Westhoff MA, Fischer-Posovszky P, Fulda S, Schanbacher M, et al. 4-hydroperoxy-cyclophosphamide mediates caspase-independent T-cell apoptosis involving oxidative stress-induced nuclear relocation of mitochondrial apoptogenic factors AIF and EndoG. Cell Death Differ 2008;15:332-43.
92. Schwartz PS, Waxman DJ. Cyclophosphamide induces caspase 9-dependent apoptosis in 9L tumor cells. Mol Pharmacol 2001;60:1268-79.
93. Viaud S, Saccheri F, Mignot G, Yamazaki T, Daillère R, et al. The intestinal microbiota modulates the anticancer immune effects of cyclophosphamide. Science 2013;342:971-6.
94. Viaud S, Flament C, Zoubir M, Pautier P, LeCesne A, et al. Cyclophosphamide induces differentiation of Th17 cells in cancer patients. Cancer Res 2011;71:661-5.
95. Daillère R, Vétizou M, Waldschmitt N, Yamazaki T, Isnard C, et al. Enterococcus hirae and Barnesiella intestinihominis facilitate cyclophosphamide-induced therapeutic immunomodulatory effects. Immunity 2016;45:931-43.
96. Geller LT, Barzily-Rokni M, Danino T, Jonas OH, Shental N, et al. Potential role of intratumor bacteria in mediating tumor resistance to the chemotherapeutic drug gemcitabine. Science 2017;357:1156-60.
97. Masotti A. Interplays between gut microbiota and gene expression regulation by miRNAs. Front Cell Infect Microbiol 2012;2:137.
98. Maudet C, Mano M, Eulalio A. MicroRNAs in the interaction between host and bacterial pathogens. FEBS Lett 2014;588:4140-7.
99. Dalmasso G, Nguyen HT, Yan Y, Laroui H, Charania MA, et al. Microbiota modulate host gene expression via microRNAs. PLoS One 2011;6:e19293.
100. Kobayashi M, Funayama R, Ohnuma S, Unno M, Nakayama K. Wnt-β-catenin signaling regulates ABCC3 (MRP3) transporter expression in colorectal cancer. Cancer Sci 2016;107:1776-84.
101. Xue X, Feng T, Yao S, Wolf KJ, Liu CG, et al. Microbiota downregulates dendritic cell expression of miR-10a, which targets IL-12/IL-23p40. J Immunol 2011;187:5879-86.
102. Mjelle R, Sjursen W, Thommesen L, Sætrom P, Hofsli E. Small RNA expression from viruses, bacteria and human miRNAs in colon cancer tissue and its association with microsatellite instability and tumor location. BMC Cancer 2019;19:161.
103. Yu T, Guo F, Yu Y, Sun T, Ma D, et al. Fusobacterium nucleatum promotes chemoresistance to colorectal cancer by modulating autophagy. Cell 2017;170:548-63.e16.
104. Dorward DW, Garon CF, Judd RC. Export and intercellular transfer of DNA via membrane blebs of Neisseria gonorrhoeae. J Bacteriol 1989;171:2499-505.
105. Brown L, Wolf JM, Prados-Rosales R, Casadevall A. Through the wall: extracellular vesicles in Gram-positive bacteria, mycobacteria and fungi. Nat Rev Microbiol 2015;13:620-30.
106. Kim JH, Lee J, Park J, Gho YS. Gram-negative and Gram-positive bacterial extracellular vesicles. Semin Cell Dev Biol 2015;40:97-104.
107. Yu YJ, Wang XH, Fan GC. Versatile effects of bacterium-released membrane vesicles on mammalian cells and infectious/inflammatory diseases. Acta Pharmacol Sin 2018;39:514-33.
108. Schwechheimer C, Kuehn MJ. Outer-membrane vesicles from Gram-negative bacteria: biogenesis and functions. Nat Rev Microbiol 2015;13:605-19.
109. Kulp A, Kuehn MJ. Biological functions and biogenesis of secreted bacterial outer membrane vesicles. Annu Rev Microbiol 2010;64:163-84.
110. Haurat MF, Aduse-Opoku J, Rangarajan M, Dorobantu L, Gray MR, et al. Selective sorting of cargo proteins into bacterial membrane vesicles. J Biol Chem 2011;286:1269-76.
111. Ghosal A, Upadhyaya BB, Fritz JV, Heintz-Buschart A, Desai MS, et al. The extracellular RNA complement of Escherichia coli. Microbiologyopen 2015;4:252-66.
112. Resch U, Tsatsaronis JA, Le Rhun A, Stübiger G, Rohde M, et al. A Two-component regulatory system impacts extracellular membrane-derived vesicle production in group A streptococcus. MBio 2016;7:e00207-16.
113. Liu S, da Cunha AP, Rezende RM, Cialic R, Wei Z, et al. The host shapes the gut microbiota via fecal microRNA. Cell Host Microbe 2016;19:32-43.
114. Azizian A, Epping I, Kramer F, Jo P, Bernhardt M, et al. Prognostic value of microRNAs in preoperative treated rectal cancer. Int J Mol Sci 2016;17:568.
115. Swanton C. Intratumor heterogeneity: evolution through space and time. Cancer Res 2012;72:4875-82.
116. Kreso A, O’Brien CA, van Galen P, Gan OI, Notta F, et al. Variable clonal repopulation dynamics influence chemotherapy response in colorectal cancer. Science 2013;339:543-8.
117. Holohan C, Van Schaeybroeck S, Longley DB, Johnston PG. Cancer drug resistance: an evolving paradigm. Nat Rev Cancer 2013;13:714-26.
118. McMillin DW, Negri JM, Mitsiades CS. The role of tumour-stromal interactions in modifying drug response: challenges and opportunities. Nat Rev Drug Discov 2013;12:217-28.
119. Sharma P, Allison JP. Immune checkpoint targeting in cancer therapy: toward combination strategies with curative potential. Cell 2015;161:205-14.
120. van Vliet MJ, Harmsen HJ, de Bont ES, Tissing WJ. The role of intestinal microbiota in the development and severity of chemotherapy-induced mucositis. PLoS Pathog 2010;6:e1000879.
121. Marthey L, Mateus C, Mussini C, Nachury M, Nancey S, et al. Cancer immunotherapy with anti-CTLA-4 monoclonal antibodies induces an inflammatory bowel disease. J Crohns Colitis 2016;10:395-401.
122. Chen JH, Pezhouh MK, Lauwers GY, Masia R. Histopathologic features of colitis due to immunotherapy with anti-PD-1 antibodies. Am J Surg Pathol 2017;41:643-54.
123. Ubeda C, Taur Y, Jenq RR, Equinda MJ, Son T, et al. Vancomycin-resistant Enterococcus domination of intestinal microbiota is enabled by antibiotic treatment in mice and precedes bloodstream invasion in humans. J Clin Invest 2010;120:4332-41.
124. Teillant A, Gandra S, Barter D, Morgan DJ, Laxminarayan R. Potential burden of antibiotic resistance on surgery and cancer chemotherapy antibiotic prophylaxis in the USA: a literature review and modelling study. Lancet Infect Dis 2015;15:1429-37.
125. Samet A, Sledzińska A, Krawczyk B, Hellmann A, Nowicki S, et al. Leukemia and risk of recurrent Escherichia coli bacteremia: genotyping implicates E. coli translocation from the colon to the bloodstream. Eur J Clin Microbiol Infect Dis 2013;32:1393-400.
126. Tulkens J, Vergauwen G, Van Deun J, Geeurickx E, Dhondt B, et al. Increased levels of systemic LPS-positive bacterial extracellular vesicles in patients with intestinal barrier dysfunction. Gut 2020;69:191-3.
127. Cavaillon JM. Exotoxins and endotoxins: inducers of inflammatory cytokines. Toxicon 2018;149:45-53.