YopH inhibits early pro-inflammatory cytokine responses during plague pneumonia
Tóm tắt
Yersinia pestis is the causative agent of pneumonic plague; recently, we and others reported that during the first 24-36 hours after pulmonary infection with Y. pestis pro-inflammatory cytokine expression is undetectable in lung tissues. Here, we report that, intranasal infection of mice with CO92 delta yopH mutant results in an early pro-inflammatory response in the lungs characterized by an increase in the pro-inflammatory cytokines Tumor Necrosis Factor-alpha and Interleukin one-beta 24 hours post-infection. CO92 delta yopH colonizes the lung but does not disseminate to the liver or spleen and is cleared from the host within 72 hours post-infection. This is different from what is observed in a wild-type CO92 infection, where pro-inflammatory cytokine expression and immune cell infiltration into the lungs is not detectable until 36-48 h post-infection. CO92 rapidly disseminates to the liver and spleen resulting in high bacterial burdens in these tissues ultimately cumulating in death 72-94 h post-infection. Mice deficient in TNF-alpha are more susceptible to CO92 delta yopH infection with 40% of the mice succumbing to infection. Altogether, our results suggest that YopH can inhibit an early pro-inflammatory response in the lungs of mice and that this is an important step in the pathogenesis of infection.
Tài liệu tham khảo
Perry RD, Fetherston JD: Yersinia pestis: etiologic agent of plague. Clin Microbiol Rev. 1997, 10: 35-66.
Dennis DT, Meier FT: Plague. Pathology of Emerging Infections. Edited by: Horsburgh CR, Nelson AM. 1997, Washington DC: American Society for Microbiology, 21-47.
Inglesby TV, et al.,: Plague as a biological weapon: medical and public health management. Working Group on Civilian Biodefense. JAMA. 2000, 283: 2281-2290. 10.1001/jama.283.17.2281.
Bubeck SS, Cantwell AM, Dube PH: Delayed inflammatory response to primary pneumonic plague occurs in both outbred and inbred mice. Infect Immun. 2007, 75: 697-705. 10.1128/IAI.00403-06.
Lathem WW, Crosby SD, Miller VL, Goldman WE: Progression of primary pneumonic plague: a mouse model of infection, pathology, and bacterial transcriptional activity. Proc Natl Acad Sci USA. 2005, 102: 17786-91. 10.1073/pnas.0506840102.
Cornelis GR, Wolf-Watz H: The Yersinia Yop virulon: a bacterial system for subverting eukaryotic cells. Mol Microbiol. 1997, 23: 861-867. 10.1046/j.1365-2958.1997.2731623.x.
Dube P: Interaction of Yersinia with the gut: mechanisms of pathogenesis and immune evasion. Curr Top Microbiol Immunol. 2009, 337: 61-91. full_text.
Viboud GI, Bliska JB: Yersinia outer proteins: role in modulation of host cell signaling responses and pathogenesis. Annu Rev Microbiol. 2005, 59: 69-89. 10.1146/annurev.micro.59.030804.121320.
Chimini G, Chavrier P: Function of Rho family proteins in actin dynamics during phagocytosis and engulfment. Nat Cell Biol. 2000, 2: E191-6. 10.1038/35036454.
May RC, Machesky LM: Phagocytosis and the actin cytoskeleton. J Cell Sci. 2001, 114: 1061-77.
Kerschen EJ, Cohen DA, Kaplan AM, Straley SC: The plague virulence protein YopM targets the innate immune response by causing a global depletion of NK cells. Infect Immun. 2004, 72: 4589-602. 10.1128/IAI.72.8.4589-4602.2004.
Black DS, Bliska JB: Identification of p130Cas as a substrate of Yersinia YopH (Yop51), a bacterial protein tyrosine phosphatase that translocates into mammalian cells and targets focal adhesions. EMBO J. 1997, 16: 2730-44. 10.1093/emboj/16.10.2730.
Montagna LG, Ivanov MI, Bliska JB: Identification of residues in the N-terminal domain of the Yersinia tyrosine phosphatase that are critical for substrate recognition. J Biol Chem. 2001, 276: 5005-11. 10.1074/jbc.M009045200.
Grosdent N, Maridonneau-Parini I, Sory MP, Cornelis GR: Role of Yops and adhesins in resistance of Yersinia enterocolitica to phagocytosis. Infect Immun. 2002, 70: 4165-76. 10.1128/IAI.70.8.4165-4176.2002.
Sauvonnet N, Lambermont I, van der Bruggen P, Cornelis GR: YopH prevents monocyte chemoattractant protein 1 expression in macrophages and T-cell proliferation through inactivation of the phosphatidylinositol 3-kinase pathway. Mol Microbiol. 2002, 45: 805-15. 10.1046/j.1365-2958.2002.03053.x.
Koyasu S: The role of PI3K in immune cells. Nat Immunol. 2003, 4: 313-9. 10.1038/ni0403-313.
Bliska JB, Guan K, Dixon JE, Falkow S: A mechanism of bacterial pathogenesis: tyrosine phosphate hydrolysis of host proteins by an essential Yersinia virulence determinant. Proc Natl Acad Sci USA. 1991, 88: 1187-1191. 10.1073/pnas.88.4.1187.
Bubeck SS, Dube PH: Yersinia pestis CO92 delta yopH is a potent live, attenuated plague vaccine. Clin Vaccine Immunol. 2007, 14: 1235-8. 10.1128/CVI.00137-07.
Fisher ML, Castillo C, Mecsas J: Intranasal inoculation of mice with Yersinia pseudotuberculosis causes a lethal lung infection that is dependent on Yersinia outer proteins and PhoP. Infect Immun. 2007, 75: 429-42. 10.1128/IAI.01287-06.
Logsdon LK, Mecsas J: The proinflammatory response induced by wild-type Yersinia pseudotuberculosis infection inhibits survival of yop mutants in the gastrointestinal tract and Peyer's patches. Infect Immun. 2006, 74: 1516-27. 10.1128/IAI.74.3.1516-1527.2006.
Trulzsch K, Sporleder T, Igwe EI, Russmann H, Heesemann J: Contribution of the major secreted yops of Yersinia enterocolitica O:8 to pathogenicity in the mouse infection model. Infect Immun. 2004, 72: 5227-34. 10.1128/IAI.72.9.5227-5234.2004.
Dube PH, Revell PA, Chaplin DD, Lorenz RG, Miller VL: A role for IL-1 alpha in inducing pathologic inflammation during bacterial infection. Proc Natl Acad Sci USA. 2001, 98: 10880-10885. 10.1073/pnas.191214498.
Dube PH, Handley SA, Lewis J, Miller VL: Protective role of interleukin-6 during Yersinia enterocolitica infection is mediated through the modulation of inflammatory cytokines. Infect Immun. 2004, 72: 3561-70. 10.1128/IAI.72.6.3561-3570.2004.
Dube PH, Handley SA, Revell PA, Miller VL: The rovA mutant of Yersinia enterocolitica displays differential degrees of virulence depending on the route of infection. Infect Immun. 2003, 71: 3512-20. 10.1128/IAI.71.6.3512-3520.2003.
Hardy RD, Coalson JJ, Peters J, Chaparro A, Techasaensiri C, Cantwell AM, Kannan TR, Baseman JB, Dube PH: Analysis of pulmonary inflammation and function in the mouse and baboon after exposure to Mycoplasma pneumoniae CARDS toxin. PLoS One. 2009, 4: e7562-10.1371/journal.pone.0007562.
Sebbane F, Gardner D, Long D, Gowen BB, Hinnebusch BJ: Kinetics of disease progression and host response in a rat model of bubonic plague. Am J Pathol. 2005, 166: 1427-39.
Cornelis GR: Yersinia type III secretion: send in the effectors. J Cell Biol. 2002, 158: 401-8. 10.1083/jcb.200205077.
Rebeil R, Ernst RK, Gowen BB, Miller SI, Hinnebusch BJ: Variation in lipid A structure in the pathogenic yersiniae. Mol Microbiol. 2004, 52: 1363-73. 10.1111/j.1365-2958.2004.04059.x.
Montminy SW, Khan N, McGrath S, Walkowicz MJ, Sharp F, Conlon JE, Fukase K, Kusumoto S, Sweet C, Miyake K, et al.,: Virulence factors of Yersinia pestis are overcome by a strong lipopolysaccharide response. Nat Immunol. 2006, 7: 1066-73. 10.1038/ni1386.
Barton ES, White DW, Cathelyn JS, Brett-McClellan KA, Engle M, Diamond MS, Miller VL, HWt Virgin: Herpesvirus latency confers symbiotic protection from bacterial infection. Nature. 2007, 447: 326-9. 10.1038/nature05762.
Black DS, Montagna LG, Zitsmann S, Bliska JB: Identification of an amino-terminal substrate-binding domain in the Yersinia tyrosine phosphatase that is required for efficient recognition of focal adhesion targets. Mol Microbiol. 1998, 29: 1263-74. 10.1046/j.1365-2958.1998.01014.x.
Bliska JB, Galan JE, Falkow S: Signal transduction in the mammalian cell during bacterial attachment and entry. Cell. 1993, 73: 903-920. 10.1016/0092-8674(93)90270-Z.
Parkhill J, Wren BW, Thomson NR, Titball RW, Holden MT, Prentice MB, Sebaihia M, James KD, Churcher C, Mungall KL., et al.,: Genome sequence of Yersinia pestis, the causative agent of plague. Nature. 2001, 413: 523-7. 10.1038/35097083.
Andrews HL, Vogel JP, Isberg RR: Identification of linked Legionella pneumophila genes essential for intracellular growth and evasion of the endocytic pathway. Infect Immun. 1998, 66: 950-8.
Merriam JJ, Mathur R, Maxfield-Boumil R, Isberg RR: Analysis of the Legionella pneumophila fliI gene: intracellular growth of a defined mutant defective for flagellum biosynthesis. Infect Immun. 1997, 65: 2497-501.
Darwin A, Miller V: Identification of Yersinia enterocolitica genes affecting survival in an animal host using signature-tagged transposon mutagenesis. Mol Microbiol. 1999, 32: 51-62. 10.1046/j.1365-2958.1999.01324.x.
Dube P, DeCostanzo A, Konopka JB: Interaction between transmembrane domains five and six of the alpha -factor receptor. J Biol Chem. 2000, 275: 26492-9. 10.1074/jbc.M002767200.
Guinet F, Carniel E: A technique of intradermal injection of Yersinia to study Y. pestis physiopathology. Adv Exp Med Biol. 2003, 529: 73-8. full_text.
Handley SA, Dube PH, Revell PA, Miller VL: Characterization of oral Yersinia enterocolitica infection in three different strains of inbred mice. Infect Immun. 2004, 72: 1645-56. 10.1128/IAI.72.3.1645-1656.2004.