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TLR4 is involved in mediating fatal murine pneumonia due to Burkholderia cenocepacia

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DOI: 10.4236/oji.2011.13012    3,284 Downloads   7,050 Views   Citations

ABSTRACT

Background: We previously showed that MyD88 knocked out mice were protected from death due to B. cenocepacia pneumonia implying that a toll-like receptor(s) (TLR) was involved in mediating death. The aim of the present study was to determine which TLR(s) was involved in triggering the inflammatory response responsible for the pathogenesis. We specifically focus on the TLRs 4 and 5, as these two receptors are the main ones involved in the recognition of P. aeruginosa, a flagellated Gram-bacterium similar to B. cenocepacia. Methods: Mice were infected intratracheally with a suspension of B. ceno-cepacia. Animals were then observed daily for signs of morbidity. Alternatively, bronchoalveolar lavages (BAL) were collected at different time points to further determine cytokine con-centrations and the number of CFU of B. ceno-cepacia. Results: The data clearly indicate that the innate immune response of the host to B. cenocepacia lung infection was due to TLR4 that senses the pathogen while TLR5 does not do so in vivo. As with the MyD88-/- strain, TLR4-/- mice were protected from death and cytokine and chemokine synthesis to infection were reduced. The only paradoxical observation was the reduced pathogen burden in the case of TLR4-/- mice compared to the enhanced (but transient) pathogen burden observed with MyD88-/- mice, suggesting that another TLR was involved in bacterial clearance. Conclusion: The data clearly demonstrate a deleterious implication of TLR4 in the host to B. cenocepacia lung infection.

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

Balloy, V. , Nagel, H. , Ramphal, R. , Si-Tahar, M. and Chignard, M. (2011) TLR4 is involved in mediating fatal murine pneumonia due to Burkholderia cenocepacia. Open Journal of Immunology, 1, 97-102. doi: 10.4236/oji.2011.13012.

References

[1] Mahenthiralingam, E., Baldwin A. and Vandamme, P. (2002) Burkholderia cepacia complex infection in patients with cystic fibrosis. Journal of Medical Microbiology, 51, 533-538.
[2] Coenye, T. and Vandamme, P. (2003) Diversity and significance of Burkholderia species occupying diverse ecological niches. Environmental Microbiology, 5, 719-729. doi:10.1046/j.1462-2920.2003.00471.x
[3] Vandamme, P., Holmes, B., Coenye, T., Goris, J., Mahenthiralingam, E., LiPuma, J.J. and Govan J.R. (2003) Burkholderia cenocepacia sp. nov.—a new twist to an old story. Research in Microbiology, 154, 91-96. doi:10.1016/S0923-2508(03)00026-3
[4] Mahenthiralingam, E. and Vandamme, P. (2005) Taxonomy and pathogenesis of the Burkholderia cepacia complex. Chronic Respiratory Disease, 2, 209-217. doi:10.1191/1479972305cd053ra
[5] Reik, R., Spilker. T. and Lipuma, J.J. (2005) Distribution of Burkholderia cepacia complex species among isolates recovered from persons with or without cystic fibrosis. Journal of Clinical Microbiology, 43, 2926-2928. doi:10.1128/JCM.43.6.2926-2928.2005
[6] Vanlaere, E., Baldwin, A., Gevers, D., Henry, D., De Brandt E., LiPuma, J.J., Mahenthiralingam, E., Speert, D.P., Dowson, C., Vandamme, P. and Taxon, K. (2009) A complex within the Burkholderia cepacia complex, comprises at least two novel species, Burkholderia contaminans sp. nov. and Burkholderia lata sp. nov. rnational Journal of Systematic and Evolutionary Microbiology, 59, 102-111.
[7] LiPuma, J.J., Spilker, T., Gill, L.H., Campbell, P.W. 3rd, Liu, L. and Mahenthiralingam, E. (2001) Disproportionate distribution of Burkholderia cepacia complex species and transmissibility markers in cystic fibrosis. American Journal of Respiratory and Critical Care Medicine, 164, 92-96.
[8] Speert, D.P., Henry, D., Vandamme, P., Corey, M. and Mahenthiralingam E. (2002) Epidemiology of Burkholderia cepacia complex in patients with cystic fibrosis, Canada. Emerging Infectious Diseases, 8, 181-187.
[9] Mahenthiralingam, E., Urban, T.A. and Goldberg, J.B. (2005) The multifarious, multireplicon Burkholderia cepacia complex. Nature Reviews Microbiology, 3, 144-156. doi:10.1038/nrmicro1085
[10] De Soyza, A., Ellis, C.D., Khan, C.M., Corris, P.A. and Demarco de Hormaeche, R. (2004) Burkholderia cenocepacia lipopolysaccharide, lipid A, and proinflammatory activity. American Journal of Respiratory and Critical Care Medicine, 170, 70-77. doi:10.1164/rccm.200304-592OC
[11] Bamford, S., Ryley, H. and Jackson S. (2007) Highly purified lipopolysaccharides from Burkholderia cepacia complex clinical isolates induce inflammatory cytokine responses via TLR4-mediated MAPK signalling pathways and activation of NFkappaB. Cellular Microbiology, 9, 532-543. doi:10.1111/j.1462-5822.2006.00808.x
[12] Zughaier, S.M., Ryley, H.C. and Jackson, S.K. (1999) Lipopolysaccharide (LPS) from Burkholderia cepacia is more active than LPS from Pseudomonas aeruginosa and Stenotrophomonas maltophilia in stimulating tumor necrosis factor alpha from human monocytes. Infection and Immunity, 67, 1505-1507.
[13] Iwamura, C. and Nakayama, T. (2008) Toll-like receptors in the respiratory system: their roles in inflammation. Current Allergy and Asthma Reports, 8, 7-13. doi:10.1007/s11882-008-0003-0
[14] Bauer, S., Müller, T. and Hamm, S. (2009) Pattern recognition by Toll-like receptors. Advances in Experimental Medicine and Biology, 653, 15-34. doi:10.1007/978-1-4419-0901-5_2
[15] Kumar, H., Kawai, T and Akira, S. (2009) Toll-like receptors and innate immunity. Biochemical and Biophysical Research Communications, 388, 621-625. doi:10.1016/j.bbrc.2009.08.062
[16] Le Goffic, R., Balloy, V., Lagranderie, M., Alexopoulou, L., Escriou, N., Flavell, R., Chignard, M. and Si-Tahar, M. (2006) Detrimental contribution of the Toll-like receptor (TLR)3 to influenza A virus-induced acute pneumonia. PLoS Pathogens, 2, e53. doi:10.1371/journal.ppat.0020053
[17] Balloy, V., Si-Tahar, M., Takeuchi, O., Philippe, B., Nahori, M.A., Tanguy, M., Huerre, M., Akira, S., Latgé, J.P. and Chignard, M. (2005) Involvement of toll-like receptor 2 in experimental invasive pulmonary aspergillosis. Infection and Immunity, 73, 5420-5425. doi:10.1128/IAI.73.9.5420-5425.2005
[18] Balloy, V. and Chignard, M. (2009) The innate immune response to Aspergillus fumigatus. Microbes and Infection, 11, 919-927. doi:10.1016/j.micinf.2009.07.002
[19] Ramphal, R., Balloy, V., Huerre, M., Si-Tahar, M. and Chignard, M. (2005) TLRs 2 and 4 are not involved in hypersusceptibility to acute Pseudomonas aeruginosa lung infections. Journal of Immunology, 175, 3927-3934.
[20] Ramphal, R., Balloy, V., Jyot, J., Verma, A., Si-Tahar, M. and Chignard, M. (2008) Control of Pseudomonas aeruginosa in the lung requires the recognition of either lipopolysaccharide or flagellin. Journal of Immunology, 181, 586-592.
[21] Raoust, E., Balloy, V., Garcia-Verdugo, I., Touqui, L., Ramphal, R. and Chignard, M. (2009) Pseudomonas aeruginosa LPS or flagellin are sufficient to activate TLR-dependent signaling in murine alveolar macrophages and airway epithelial cells. PLoS One, 4, e7259. doi:10.1371/journal.pone.0007259
[22] Ventura, G.M., Balloy, V., Ramphal, R., Khun, H., Huerre, M., Ryffel, B., Plotkowski, M.C., Chignard, M. and Si-Tahar, M. (2009) Lack of MyD88 protects the immunodeficient host against fatal lung inflammation triggered by the opportunistic bacteria Burkholderia cenocepacia. Journal of Immunology, 183, 670-676. doi:10.4049/jimmunol.0801497
[23] Feuillet, V., Medjane, S., Mondor, I., Demaria, O., Pagni, P.P., Galán, J.E., Flavell, R.A. and Alexopoulou, L. (2006) Involvement of Toll-like receptor 5 in the recognition of flagellated bacteria. Proceedings of the National Academy of Sciences of the United States of America, 103, 12487-12492. doi:10.1073/pnas.0605200103
[24] Skerrett, S.J., Wilson, C.B., Liggitt, H.D. and Hajjar, A.M. (2007) Redundant Toll-like receptor signaling in the pulmonary host response to Pseudomonas aeruginosa. American Journal of Physiology—Lung Cellular and Molecular Physiology, 292, L312-L322. doi:10.1152/ajplung.00250.2006
[25] Morris, A.E., Liggitt, H.D., Hawn, T.R. and Skerrett, S.J. (2009) Role of Toll-like receptor 5 in the innate immune response to acute P. aeruginosa pneumonia. American Journal of Physiology—Lung Cellular and Molecular Physiology, 297, L1112-L1119. doi:10.1152/ajplung.00155.2009
[26] Balloy, V., Sallenave, J.M., Crestani, B., Dehoux, M. and Chignard, M. (2003) Neutrophil DNA contributes to the antielastase barrier during acute lung inflammation. American Journal of Respiratory Cell and Molecular Biology, 28, 746-753. doi:10.1165/rcmb.2002-0119OC
[27] Gon?alves de Moraes, V.L., Singer, M., Vargaftig, B.B. and Chignard, M. (1998) Effects of rolipram on cyclic AMP levels in alveolar macrophages and lipopolysaccharide-induced inflammation in mouse lung. British Journal of Pharmacology, 123, 631-636. doi:10.1038/sj.bjp.0701649
[28] de C Ventura, G.M., Le Goffic, R., Balloy, V., Plotkowski, M.C., Chignard, M. and Si-Tahar, M. (2008) TLR 5, but neither TLR2 nor TLR4, is involved in lung epithelial cell response to Burkholderia cenocepacia. FEMS Immunology & Medical Microbiology, 54, 37-44. doi:10.1111/j.1574-695X.2008.00453.x
[29] Urban, T.A., Griffith, A., Torok, A.M., Smolkin, M.E., Burns, J.L. and Goldberg, J.B. (2004) Contribution of Burkholderia cenocepacia flagella to infectivity and inflammation. Infection and Immunity, 72, 5126-5134. doi:10.1128/IAI.72.9.5126-5134.2004
[30] Akerley, B.J., Cotter, P.A. and Miller, JF. (1995) Ectopic expression of the flagellar regulon alters development of Bordetella-host interaction. Cell, 80, 611-620. doi:10.1016/0092-8674(95)90515-4

  
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