Burkholderia pseudomallei, a gram-negative intracellular bacterium, is a causative agent of melioidosis. The bacterium has been shown to induce the innate immune response, particularly pro-inflammatory cytokine production in several of both mouse and human cell types. In the present study, we investigate host immune response in B. pseudomallei-infected primary human monocytes. We discover that wild-type B. pseudomallei is able to survive and multiply inside the primary human monocytes. In contrast, B. pseudomallei LPS mutant, a less virulent strain, is susceptible to host killing during bacterial infection. Moreover, microarray result showed that wild-type B. pseudomallei but not B. pseudomallei LPS mutant is able to activate gene expression of IL-23 as demonstrated by the up-regulation of p19 and p40 subunit expression. Consistent with gene expression analysis, the secretion of IL-23 analyzed by ELISA also showed that wild-type B. pseudomallei induces a significantly higher level of IL-23 secretion than that of B. pseudomallei LPS mutant. These results implied that IL-23 may be an important cytokine for the innate immune response during B. pseudomallei infection. The regulation of IL-23 production may drive the different host innate immune responses between patients and may relate to the severity of melioidosis.
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Wiersinga WJ, van der Poll T, White NJ, Day NP, Peacock SJ (2006) Melioidosis: insights into the pathogenicity of Burkholderia pseudomallei. Nat Rev Microbiol 4:272–282
Jones AL, Beveridge TJ, Woods DE (1996) Intracellular survival of Burkholderia pseudomallei. Infect Immun 64:782–790
Harley VS, Dance DA, Drasar BS, Tovey G (1998) Effects of Burkholderia pseudomallei and other Burkholderia species on eukaryotic cells in tissue culture. Microbios 96:71–93
Kespichayawattana W, Rattanachetkul S, Wanun T, Utaisincharoen P, Sirisinha S (2000) Burkholderia pseudomallei induces cell fusion and actin-associated membrane protrusion: a possible mechanism for cell-to-cell spreading. Infect Immun 68:5377–5384
Breitbach K, Rottner K, Klocke S, Rohde M, Jenzora A, Wehland J, Steinmetz I (2003) Actin-based motility of Burkholderia pseudomallei involves the Arp 2/3 complex, but not N-WASP and Ena/VASP proteins. Cell Microbiol 5:385–393
Suparak S, Muangsombut V, Riyapa D, Stevens JM, Stevens MP, Lertmemongkolchai G, Korbsrisate S (2011) Burkholderia pseudomallei-induced cell fusion in U937 macrophages can be inhibited by monoclonal antibodies against host cell surface molecules. Microbes Infect 13:1006–1011
Ulett GC, Ketheesan N, Hirst RG (2000) Cytokine gene expression in innately susceptible BALB/c mice and relatively resistant C57BL/6 mice during infection with virulent Burkholderia pseudomallei. Infect Immun 68:2034–2042
Wiersinga WJ, Dessing MC, Kager PA et al (2007) High-throughput mRNA profiling characterizes the expression of inflammatory molecules in sepsis caused by Burkholderia pseudomallei. Infect Immun 75:3074–3079
Haque A, Easton A, Smith D et al (2006) Role of T cells in innate and adaptive immunity against murine Burkholderia pseudomallei infection. J Infect Dis 193:370–379
Gan YH (2005) Interaction between Burkholderia pseudomallei and the host immune response: sleeping with the enemy? J Infect Dis 192:1845–1850
Ulett GC, Ketheesan N, Hirst RG (2000) Proinflammatory cytokine mRNA responses in experimental Burkholderia pseudomallei infection in mice. Acta Trop 74:229–234
Pongcharoen S, Niumsup PR, Butkhamchot P (2008) Comparative study of interleukin-1beta expression by peripheral blood mononuclear cells and purified monocytes experimentally infected with Burkholderia pseudomallei and Burkholderia thailandensis. Immunol Invest 37(7):704–713
Verreck FA, de Boer T, Langenberg DM et al (2004) Human IL-23-producing type 1 macrophages promote but IL-10-producing type 2 macrophages subvert immunity to (myco)bacteria. Proc Natl Acad Sci USA 101:4560–4565
Kim BJ, Lee S, Berg RE, Simecka JW, Jones HP (2013) Interleukin-23 (IL-23) deficiency disrupts Th17 and Th1-related defenses against Streptococcus pneumoniae infection. Cytokine 64:375–381
Arjcharoen S, Wikraiphat C, Pudla M et al (2007) Fate of a Burkholderia pseudomallei lipopolysaccharide mutant in the mouse macrophage cell line RAW264.7: possible role for the O-antigenic polysaccharide moiety of lipopolysaccharide in internalization and intracellular survival. Infect Immun 75(9):4298–4304
Wikraiphat C, Charoensap J, Utaisincharoen P et al (2009) Comparative in vivo and in vitro analyses of putative virulence factors of Burkholderia pseudomallei using lipopolysaccharide, capsule and flagellin mutants. FEMS Immunol Med Microbiol 56:253–259
Charoensap J, Utaisincharoen P, Engering A, Sirisinha S (2009) Differential intracellular fate of Burkholderia pseudomallei 844 and Burkholderia thailandensis UE5 in human monocyte-derived dendritic cells and macrophages. BMC Immunol 10:20
Wikraiphat C, Pudla M, Baral P, Kitthawee S, Utaisincharoen P (2014) Activation of NADPH oxidase is essential, but not sufficient, in controlling intracellular multiplication of Burkholderia pseudomallei in primary human monocytes. Pathog Dis 71(1):69–72
DeShazer D, Brett PJ, Woods DE (1998) The type II O-antigenic polysaccharide moiety of Burkholderia pseudomallei lipopolysaccharide is required for serum resistance and virulence. Mol Microbiol 30:1081–1100
Ma XT, Zhang XJ, Zhang B, Geng YQ, Lin YM, Li G, Wu KF (2004) Expression and regulation of interleukin-23 subunits in human peripheral blood mononuclear cells and hematopoietic cell lines in response to various inducers. Cell Biol Int 28:689–697
Utaisincharoen P, Tangthawornchaikul N, Kespichayawattana W, Anuntagool N, Chaisuriya P, Sirisinha S (2000) Kinetic studies of the production of nitric oxide (NO) and tumour necrosis factor-alpha (TNF-alpha) in macrophages stimulated with Burkholderia pseudomallei endotoxin. Clin Exp Immunol 122:324–329
Duvallet E, Semerano L, Assier E, Falgarone G, Boissier MC (2011) Interleukin-23: a key cytokine in inflammatory diseases. Ann Med 43:503–511
Holscher C (2004) The power of combinatorial immunology: IL-12 and IL-12-related dimeric cytokines in infectious diseases. Med Microbiol Immunol 193:1–17
Butchar JP, Rajaram MV, Ganesan LP, Parsa KV, Clay CD, Schlesinger LS, Tridandapani S (2007) Francisella tularensis induces IL-23 production in human monocytes. J Immunol 178:4445–4454
McKenzie BS, Kastelein RA, Cua DJ (2006) Understanding the IL-23-IL-17 immune pathway. Trends Immunol 27:17–23
Langrish CL, McKenzie BS, Wilson NJ, de Waal Malefyt R, Kastelein RA, Cua DJ (2004) IL-12 and IL-23: master regulators of innate and adaptive immunity. Immunol Rev 202:96–105
Beadling C, Slifka MK (2006) Regulation of innate and adaptive immune responses by the related cytokines IL-12, IL-23, and IL-27. Arch Immunol Ther Exp (Warsz) 54:15–24
Tan ZY, Bealgey KW, Fang Y, Gong YM, Bao S (2009) Interleukin-23: immunological roles and clinical implications. Int J Biochem Cell Biol 41:733–735
van de Wetering D, de Paus RA, van Dissel JT, van de Vosse E (2009) Salmonella induced IL-23 and IL-1beta allow for IL-12 production by monocytes and Mphi1 through induction of IFN-gamma in CD56 NK/NK-like T cells. PLoS One 4:e8396
Aggarwal S, Ghilardi N, Xie MH, de Sauvage FJ, Gurney AL (2003) Interleukin-23 promotes a distinct CD4 T cell activation state characterized by the production of interleukin-17. J Biol Chem 278:1910–1914
Meeks KD, Sieve AN, Kolls JK, Ghilardi N, Berg RE (2009) IL-23 is required for protection against systemic infection with Listeria monocytogenes. J Immunol 183:8026–8034
Indramohan M, Sieve AN, Break TJ, Berg RE (2012) Inflammatory monocyte recruitment is regulated by interleukin-23 during systemic bacterial infection. Infect Immun 80:4099–4105
Happel KI, Dubin PJ, Zheng M et al (2005) Divergent roles of IL-23 and IL-12 in host defense against Klebsiella pneumoniae. J Exp Med 202:761–769
This work was supported by research grants from Thailand Research Fund (TRF, Thailand) and Faculty of Science, Mahidol University (Thailand). We thank Prof. Dr. D.E. Woods (Department of Microbiology and Infectious Diseases, the University of Calgary Health Sciences Center, Calgary, Alberta, Canada) for providing wild-type B. pseudomallei (1026b) and B. pseudomallei LPS mutant (SRM117). SD is grateful for the support of a Wellcome Trust Intermediate Clinical Fellowship award ref WT100174AIA. NC was supported by the Wellcome Trust [087769/Z/08/Z].
Conflict of interest
All authors have no financial or commercial conflict of interest to declare.
For all human blood collections were conformed to the ethical standards guidelines of the Declaration of Helsinki and were approved by the human subjects committees. Ethical clearance for the human blood collection was obtained by the Ethical Committee of Ramathibodi Hospital, Mahidol University, Bangkok, Thailand (Ethical clearance number MURA 2011/607).
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Kulsantiwong, P., Pudla, M., Boondit, J. et al. Burkholderia pseudomallei induces IL-23 production in primary human monocytes. Med Microbiol Immunol 205, 255–260 (2016). https://doi.org/10.1007/s00430-015-0440-z
- B. pseudomallei
- Human monocytes