Induction of Type I Interferon Signaling Determines the Relative Pathogenicity of Strains

English version České info

The tremendous success of S. aureus as a human pathogen has been explained primarily by its array of virulence factors that enable the organism to evade host immunity. Perhaps equally important, but less well understood, is the importance of the intensity of the host response in determining the extent of pathology induced by S. aureus infection, particularly in the pathogenesis of pneumonia. We compared the pathogenesis of infection caused by two phylogenetically and epidemiologically distinct strains of S. aureus whose behavior in humans has been well characterized. Induction of the type I IFN cascade by strain 502A, due to a NOD2-IRF5 pathway, was the major factor in causing severe pneumonia and death in a murine model of pneumonia and was associated with autolysis and release of peptidogylcan. In contrast to USA300, 502A was readily eliminated from epithelial surfaces in vitro. Nonetheless, 502A caused significantly increased tissue damage due to the organisms that were able to invade systemically and trigger type I IFN responses, and this was ameliorated in Ifnar^-/- mice. The success of USA300 to cause invasive infection appears to depend upon its resistance to eradication from epithelial surfaces, but not production of specific toxins. Our studies illustrate the important and highly variable role of type I IFN signaling within a species and suggest that targeted immunomodulation of specific innate immune signaling cascades may be useful to prevent the excessive morbidity associated with S. aureus pneumonia.

Vyšlo v časopise: Induction of Type I Interferon Signaling Determines the Relative Pathogenicity of Strains. PLoS Pathog 10(2): e32767. doi:10.1371/journal.ppat.1003951
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1003951

Souhrn

Zdroje

1. ChertowDS, MemoliMJ (2013) Bacterial coinfection in influenza: a grand rounds review. JAMA 309: 275–282.

2. DiepBA, GillSR, ChangRF, PhanTH, ChenJH, et al. (2006) Complete genome sequence of USA300, an epidemic clone of community-acquired meticillin-resistant Staphylococcus aureus. Lancet 367: 731–739.

3. OttoM (2012) MRSA virulence and spread. Cell Microbiol 14: 1513–1521.

4. ChambersHF, DeleoFR (2009) Waves of resistance: Staphylococcus aureus in the antibiotic era. Nat Rev Microbiol 7: 629–641.

5. KlevensRM, MorrisonMA, NadleJ, PetitS, GershmanK, et al. (2007) Invasive methicillin-resistant Staphylococcus aureus infections in the United States. JAMA 298: 1763–1771.

6. HuangSS, SeptimusE, KleinmanK, MoodyJ, HickokJ, et al. (2013) Targeted versus universal decolonization to prevent ICU infection. N Engl J Med 368: 2255–2265.

7. ParkerD, PrinceA (2011) Innate immunity in the respiratory epithelium. Am J Respir Cell Mol Biol 45: 189–201.

8. ParkerD, PrinceA (2012) Immunopathogenesis of Staphylococcus aureus pulmonary infection. Semin Immunopathol 34: 281–297.

9. MartinFJ, GomezMI, WetzelDM, MemmiG, O'SeaghdhaM, et al. (2009) Staphylococcus aureus activates type I IFN signaling in mice and humans through the Xr repeated sequences of protein A. J Clin Invest 119: 1931–1939.

10. ParkerD, PrinceA (2012) Staphylococcus aureus induces type I IFN signaling in dendritic cells via TLR9. J Immunol 189: 4040–4046.

11. ParkerD, PrinceA (2011) Type I interferon response to extracellular bacteria in the airway epithelium. Trends Immunol 32: 582–588.

12. MonroeKM, McWhirterSM, VanceRE (2010) Induction of type I interferons by bacteria. Cell Microbiol 12: 881–890.

13. RathinamVA, FitzgeraldKA (2011) Cytosolic surveillance and antiviral immunity. Curr Opin Virol 1: 455–462.

14. ShinefieldHR, RibbleJC, EichenwaldHF, BorisM, SutherlandJM (1963) Bacterial interference: its effect on nursery-acquired infection with Staphylococcus aureus. V. An analysis and interpretation. Am J Dis Child 105: 683–688.

15. LightIJ, WaltonRL, SutherlandJM, ShinefieldHR, BrackvogelV (1967) Use of bacterial interference to control a staphylococcal nursery outbreak. Deliberate colonization of all infants with the 502A strain of Staphylococcus aureus. Am J Dis Child 113: 291–300.

16. ShinefieldHR, RibbleJC, BorisM, EichenwaldHF (1963) Bacterial interference: its effect on nursery-acquired infection with Staphylococcus aureus. I. Preliminary observations on artificial colonzation of newborns. Am J Dis Child 105: 646–654.

17. AlyR, MaibachHI, ShinefieldHR, MandelA, StraussWG (1974) Bacterial interference among strains of Staphylococcus aureus in man. J Infect Dis 129: 720–724.

18. HouckPW, NelsonJD, KayJL (1972) Fatal septicemia due to Staphylococcus aureus 502A. Report of a case and review of the infectious complications of bacterial interference programs. Am J Dis Child 123: 45–48.

19. BlairEB, TullAH (1969) Multiple infections among newborns resulting from colonization with Staphylococcus aureus 502A. Am J Clin Pathol 52: 42–49.

20. BorisM (1968) Bacterial interference: protection against staphylococcal disease. Bull N Y Acad Med 44: 1212–1221.

21. SieradzkiK, LeskiT, DickJ, BorioL, TomaszA (2003) Evolution of a vancomycin-intermediate Staphylococcus aureus strain in vivo: multiple changes in the antibiotic resistance phenotypes of a single lineage of methicillin-resistant S. aureus under the impact of antibiotics administered for chemotherapy. J Clin Microbiol 41: 1687–1693.

22. KurodaM, OhtaT, UchiyamaI, BabaT, YuzawaH, et al. (2001) Whole genome sequencing of meticillin-resistant Staphylococcus aureus. Lancet 357: 1225–1240.

23. ThurlowLR, JoshiGS, ClarkJR, SpontakJS, NeelyCJ, et al. (2013) Functional modularity of the arginine catabolic mobile element contributes to the success of USA300 methicillin-resistant Staphylococcus aureus. Cell Host Microbe 13: 100–107.

24. Planet PJ, Larussa SJ, Dana A, Smith H, Xu A, et al.. (2013) Emergence of the Epidemic Methicillin-Resistant Staphylococcus aureus Strain USA300 Coincides with Horizontal Transfer of the Arginine Catabolic Mobile Element and speG-mediated Adaptations for Survival on Skin. MBio 4..

25. MaciaE, EhrlichM, MassolR, BoucrotE, BrunnerC, et al. (2006) Dynasore, a cell-permeable inhibitor of dynamin. Dev Cell 10: 839–850.

26. BowmanEJ, SiebersA, AltendorfK (1988) Bafilomycins: a class of inhibitors of membrane ATPases from microorganisms, animal cells, and plant cells. Proc Natl Acad Sci U S A 85: 7972–7976.

27. Tigno-AranjuezJT, AsaraJM, AbbottDW (2010) Inhibition of RIP2's tyrosine kinase activity limits NOD2-driven cytokine responses. Genes Dev 24: 2666–2677.

28. LeberJH, CrimminsGT, RaghavanS, Meyer-MorseNP, CoxJS, et al. (2008) Distinct TLR- and NLR-mediated transcriptional responses to an intracellular pathogen. PLoS Pathog 4: e6.

29. PandeyAK, YangY, JiangZ, FortuneSM, CoulombeF, et al. (2009) NOD2, RIP2 and IRF5 play a critical role in the type I interferon response to Mycobacterium tuberculosis. PLoS Pathog 5: e1000500.

30. SabbahA, ChangTH, HarnackR, FrohlichV, TominagaK, et al. (2009) Activation of innate immune antiviral responses by Nod2. Nat Immunol 10: 1073–1080.

31. KobayashiK, InoharaN, HernandezLD, GalanJE, NunezG, et al. (2002) RICK/Rip2/CARDIAK mediates signalling for receptors of the innate and adaptive immune systems. Nature 416: 194–199.

32. GirardinSE, BonecaIG, VialaJ, ChamaillardM, LabigneA, et al. (2003) Nod2 is a general sensor of peptidoglycan through muramyl dipeptide (MDP) detection. J Biol Chem 278: 8869–8872.

33. TrayerHR, BuckleyCE3rd (1970) Molecular properties of lysostaphin, a bacteriolytic agent specific for Staphylococcus aureus. J Biol Chem 245: 4842–4846.

34. PesantiEL, NugentKM (1985) Modulation of pulmonary clearance of bacteria by antioxidants. Infect Immun 48: 57–61.

35. NugentKM, OnofrioJM (1987) Effect of alkylating agents on the clearance of Staphylococcus aureus from murine lungs. J Leukoc Biol 41: 78–82.

36. PetersonPK, VerhoefJ, SabathLD, QuiePG (1976) Extracellular and bacterial factors influencing staphylococcal phagocytosis and killing by human polymorphonuclear leukocytes. Infect Immun 14: 496–501.

37. SoongG, MartinFJ, ChunJR, CohenTS, AhnDS, et al. (2011) Staphylococcus aureus Protein A Mediates Invasion across Airway Epithelial Cells through Activation of RhoA GTPase Signaling and Proteolytic Activity. Journal of Biological Chemistry 286: 35891–35898.

38. SoongG, ChunJ, ParkerD, PrinceA (2012) Staphylococcus aureus activation of caspase 1/calpain signaling mediates invasion through human keratinocytes. J Infect Dis 205: 1571–1579.

39. JoshiGS, SpontakJS, KlapperDG, RichardsonAR (2011) Arginine catabolic mobile element encoded speG abrogates the unique hypersensitivity of Staphylococcus aureus to exogenous polyamines. Mol Microbiol 82: 9–20.

40. BiswasR, VogguL, SimonUK, HentschelP, ThummG, et al. (2006) Activity of the major staphylococcal autolysin Atl. FEMS Microbiol Lett 259: 260–268.

41. HugotJP, ChamaillardM, ZoualiH, LesageS, CezardJP, et al. (2001) Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease. Nature 411: 599–603.

42. OguraY, BonenDK, InoharaN, NicolaeDL, ChenFF, et al. (2001) A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease. Nature 411: 603–606.

43. StroberW, WatanabeT (2011) NOD2, an intracellular innate immune sensor involved in host defense and Crohn's disease. Mucosal Immunol 4: 484–495.

44. SoongG, ParkerD, MagargeeM, PrinceAS (2008) The type III toxins of Pseudomonas aeruginosa disrupt epithelial barrier function. J Bacteriol 190: 2814–2821.

45. ParkerD, MartinFJ, SoongG, HarfenistBS, AguilarJL, et al. (2011) Streptococcus pneumoniae DNA initiates type I interferon signaling in the respiratory tract. MBio 2: e00016–00011.

46. ChiuJC, LeeEK, EganMG, SarkarIN, CoruzziGM, et al. (2006) OrthologID: automation of genome-scale ortholog identification within a parsimony framework. Bioinformatics 22: 699–707.

47. FelsensteinJ (1985) Confidence limits on phylogenies: an approach using the bootstrap. Evolution 39: 783–791.

48. SchlagM, BiswasR, KrismerB, KohlerT, ZollS, et al. (2010) Role of staphylococcal wall teichoic acid in targeting the major autolysin Atl. Mol Microbiol 75: 864–873.