Neutrophil Crawling in Capillaries; A Novel Immune Response to
Methicillin-resistant Staphylococcus aureus (MRSA) is a highly virulent pathogen responsible for a significant portion of skin and soft tissue infections throughout the world. We investigated the role of neutrophils in soft tissue infections, as these immune cells have been shown to be both essential for clearance of this pathogen but also for increasing tissue injury associated with S. aureus infections. We visualized the behaviour of neutrophils in the subcutaneous tissue following the introduction of a localized infectious stimulus. In addition to a profound neutrophil recruitment into the infectious nidus, significant neutrophil crawling in capillaries surrounding the region was also noted, a region of vasculature which has not previously been associated with neutrophil recruitment during infection. The neutrophils were not seen to emigrate from the capillaries but rather were retained in these vessels and maintained a crawling behaviour via β2 and α4 integrins. Blocking these integrins released the neutrophils from the capillaries, reinstituted capillary perfusion, and reduced the surrounding cell death leading to reduced lesion size following infection. Neutrophil crawling within capillaries during MRSA soft tissue infections, while potentially contributing to walling off or preventing dissemination of the pathogen, resulted in impaired perfusion and increased tissue injury.
Vyšlo v časopise:
Neutrophil Crawling in Capillaries; A Novel Immune Response to. PLoS Pathog 10(10): e32767. doi:10.1371/journal.ppat.1004379
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.ppat.1004379
Souhrn
Methicillin-resistant Staphylococcus aureus (MRSA) is a highly virulent pathogen responsible for a significant portion of skin and soft tissue infections throughout the world. We investigated the role of neutrophils in soft tissue infections, as these immune cells have been shown to be both essential for clearance of this pathogen but also for increasing tissue injury associated with S. aureus infections. We visualized the behaviour of neutrophils in the subcutaneous tissue following the introduction of a localized infectious stimulus. In addition to a profound neutrophil recruitment into the infectious nidus, significant neutrophil crawling in capillaries surrounding the region was also noted, a region of vasculature which has not previously been associated with neutrophil recruitment during infection. The neutrophils were not seen to emigrate from the capillaries but rather were retained in these vessels and maintained a crawling behaviour via β2 and α4 integrins. Blocking these integrins released the neutrophils from the capillaries, reinstituted capillary perfusion, and reduced the surrounding cell death leading to reduced lesion size following infection. Neutrophil crawling within capillaries during MRSA soft tissue infections, while potentially contributing to walling off or preventing dissemination of the pathogen, resulted in impaired perfusion and increased tissue injury.
Zdroje
1. WertheimHF, MellesDC, VosMC, van LeeuwenW, van BelkumA, et al. (2005) The role of nasal carriage in Staphylococcus aureus infections. Lancet 5: 751–762.
2. MillerLS, ChoJS (2011) Immunity against Staphylococcus aureus cutaneous infections. Nat Rev Immunol 11: 505–518.
3. MoranGJ, KrishnadasanA, GorwitzRJ, FosheimGE, McDougalLK, et al. (2006) Methicillin-Resistant Staphylococcus aureus infections among patients in the emergency department. N Engl J Med 355: 666–674.
4. YamamotoT, NishiyamaA, TakanoT, YabeS, HiguchiW, et al. (2010) Community-acquired methicillin-resistant Staphylococcus aureus: Community transmission, pathogenesis, and drug resistance. J Infect Chemother 16: 225–254.
5. KingMD, HumphreyBJ, WangYF, KourbatovaEV, RaySM, et al. (2006) Emergence of community-acquired methicillin-resistant Staphylococcus aureus USA 300 clone as the predominant cause of skin and soft-tissue infections. Ann Intern Med 144: 309–317.
6. TenoverFC, GoeringRV (2009) Methicillin-resistant Staphylococcus aureus strain USA300: Origin and epidemiology. Journal of Antimicrobial Chemotherapy 64: 441–446.
7. SimorAE, GilbertNL, GravelD, MulveyMR, BryceE, et al. (2010) Methicillin Resistant Staphylococcus aureus colonization or infection in canada: National surveillance and changing epidemiology, 1995–2007. Infect Control Hosp Epidemiol 31: 348–356.
8. WilmerA, Lloyd-SmithE, RomneyM, HoangL, HullM, et al. (2011) Methicillin-resistant Staphylococcus aureus strain USA300 is prevalent among hospital-onset cases in an urban canadian setting. Infect Control Hosp Epidemiol 32: 1227–1229.
9. NippeN, VargaG, HolzingerD, LofflerB, MedinaE, et al. (2011) Subcutaneous infection with Staphylococcus aureus in mice reveals association of resistance with influx of neutrophils and Th2 response. J Invest Dermatol 131: 125–132.
10. LieseJ, RooijakkersSHM, van Strijp, JosAG, NovickRP, DustinML (2013) Intravital two-photon microscopy of host-pathogen interactions in a mouse model of Staphylococcus aureus skin abscess formation. Cell Microbiol 15: 891–909.
11. RigbyK, DeLeoF (2012) Neutrophils in innate host defense against Staphylococcus aureus infections. Semin immunopathol 34: 237–259.
12. MolneL, VerdrenghM, TarkowskiA (2000) Role of neutrophil leukocytes in cutaneous infection caused by Staphylococcus aureus. Infect Immun 68: 6162–6167.
13. ClarkSR, MaAC, TavenerSA, McDonaldB, GoodarziZ, et al. (2007) Platelet TLR4 activates neutrophil extracellular traps to ensnare bacteria in septic blood. Nat Med 13: 463–469.
14. HoffmannMH, BrunsH, BäckdahlL, NeregårdP, NiederreiterB, et al. (2012) The cathelicidins LL-37 and rCRAMP are associated with pathogenic events of arthritis in humans and rats. Annals of the Rheumatic Diseases, Ann Rheum Dis 72: 1239–1248.
15. MoraesT, ZurawskaJ, DowneyG (2006) Neutrophil granule contents in the pathogenesis of lung injury. Curr Op Hema 13: 21–27.
16. GreshamHD, LowranceJH, CaverTE, WilsonBS, CheungAL, et al. (2000) Survival of staphylococcus aureus inside neutrophils contributes to infection. The Journal of Immunology 164: 3713–3722.
17. ThwaitesGE, GantV (2011) Are bloodstream leukocytes trojan horses for the metastasis of Staphylococcus aureus? Nat Rev Micro 9: 215–222.
18. KimM, GranickJL, KwokC, WalkerNJ, BorjessonDL, et al. (2011) Neutrophil survival and c-kit+-progenitor proliferation in Staphylococcus aureus infected skin wounds promote resolution. Blood 117: 3343–3352.
19. SchmidtS, MoserM, SperandioM (2013) The molecular basis of leukocyte recruitment and its deficiencies. Mol Immunol 55: 49–58.
20. PhillipsonM, HeitB, ColarussoP, LiuL, BallantyneCM, et al. (2006) Intraluminal crawling of neutrophils to emigration sites: A molecularly distinct process from adhesion in the recruitment cascade. J Exp Med 203: 2569–2575.
21. KadiogluA, De FilippoK, BangertM, FernandesVE, RichardsL, et al. (2011) The integrins mac-1 and α4β1 perform crucial roles in neutrophil and T cell recruitment to lungs during Streptococcus pneumoniae infection. J Immunol 186: 5907–5915.
22. IbbotsonGC, DoigC, KaurJ, GillV, OstrovskyL, et al. (2001) Functional (alpha)4-integrin: A newly identified pathway of neutrophil recruiment in critically ill septic patients. Nat Med 7: 465–470.
23. PetriB, PhillipsonM, KubesP (2008) The physiology of leukocyte recruitment: An in vivo perspective. J Immunol 180: 6439–6446.
24. KolaczkowskaE, KubesP (2013) Neutrophil recruitment and function in health and inflammation. Nat Rev Immunol 13: 159–175.
25. YoongP, PierGB (2010) Antibody-mediated enhancement of community-acquired methicillin-resistant Staphylococcus aureus infection. Proc Natl Acad Sci USA 107: 2241–2246.
26. FordCW, HamelJC, StapertD, YanceyRJ (1989) Establishment of an experimental model of a Staphylococcus aureus abscess in mice by use of dextran and gelatin microcarriers. J Med Microbiol 28: 259–266.
27. NobleWC (1965) The production of subcutaneous staphylococcal skin lesions in mice. Br J Exp Pathol 46: 254–262.
28. BegierEM, FrenetteK, BarrettNL, MsharP, PetitS, et al. (2004) A high-morbidity outbreak of methicillin-resistant Staphylococcus aureus among players on a college football team, facilitated by cosmetic body shaving and turf burns. Clin Infect Dis 39: 1446–1453.
29. DaleyJM, ThomayAA, ConnollyMD, ReichnerJS, AlbinaJE (2008) Use of Ly6G-specific monoclonal antibody to deplete neutrophils in mice. J Leukoc Biol 83: 64–70.
30. MattssonE, HeyingR, GevelVD, HartungT, BeekhuizenH (2008) Staphylococcal peptidoglycan initiates an inflammatory response and procoagulant activity in human vascular endothelial cells: A comparison with highly purified lipoteichoic acid and TSST-1. FEMS Immunol Med Microbiol 52: 110–117.
31. UddinMN, McLeanLB, HunterFA, HorvatD, SeversonJ, et al. (2009) Vascular leak in a rat model of preeclampsia. Am J Nephrol 30: 26–33.
32. KruegerM, HartigW, ReichenbachA, BechmannI, MichalskiD (2013) Blood-brain barrier breakdown after embolic stroke in rats occurs without ultrastructural evidence for disrupting tight junctions. PLoS ONE 8: e56419.
33. MillerLS, PietrasEM, UricchioLH, HiranoK, RaoS, et al. (2007) Inflammasome-mediated production of IL-1β is required for neutrophil recruitment against Staphylococcus aureus in vivo. J Immunol 179: 6933–6942.
34. RobertsonCM, PerroneEE, McConnellKW, DunneWM, BoodyB, et al. (2008) Neutrophil depletion causes a fatal defect in murine pulmonary Staphylococcus aureus clearance. J Surg Res 150: 278–285.
35. PostmaB, PoppelierMJ, van GalenJC, ProssnitzER, van StrijpJAG, et al. (2004) Chemotaxis inhibitory protein of Staphylococcus aureus binds specifically to the C5a and formylated peptide receptor. J Immunol 172: 6994–7001.
36. BestebroerJ, PoppelierMJJG, UlfmanLH, LentingPJ, DenisCV, et al. (2007) Staphylococcal superantigen-like 5 binds PSGL-1 and inhibits P-selectin mediated neutrophil rolling. Blood 109: 2936–2943.
37. MillerLS, O'ConnellRM, GutierrezMA, PietrasEM, ShahangianA, et al. (2006) MyD88 mediates neutrophil recruitment initiated by IL-1R but not TLR2 activation in immunity against Staphylococcus aureus. Immunity 24: 79–91.
38. WangR, BraughtonKR, KretschmerD, BachTL, QueckSY, et al. (2007) Identification of novel cytolytic peptides as key virulence determinants for community-associated MRSA. Nat Med 13: 1510–1514.
39. KennedyAD, WardenburgJB, GardnerDJ, LongD, WhitneyAR, et al. (2010) Targeting of alpha-hemolysin by active or passive immunization decreases severity of USA300 skin infection in a mouse model. J Infect Dis 202: 1050–1058.
40. KobayashiSD, MalachowaN, WhitneyAR, BraughtonKR, GardnerDJ, et al. (2011) Comparative analysis of USA300 virulence determinants in a rabbit model of skin and soft tissue infection. J Infect Dis 204: 937–941.
41. LuissintA, LutzPG, CalderwoodDA, CouraudP, BourdoulousS (2008) JAM-l–mediated leukocyte adhesion to endothelial cells is regulated in cis by a4ß1 integrin activation. J Cell Biol 183: 1159–1173.
42. MizgerdJP, KuboH, KutkoskiGJ, BhagwanSD, Scharffetter-KochanekK, et al. (1997) Neutrophil emigration in the skin, lungs, and peritoneum: Different requirements for CD11/CD18 revealed by CD18-deficient mice. J Exp Med 186: 1357–1364.
43. JohnstonB, CheeA, IssekutzTB, UgarovaT, Fox-RobichaudA, et al. (2000) A4 integrin-dependent leukocyte recruitment does not require VCAM-1 in a chronic model of inflammation. The Journal of Immunology 164: 3337–3344.
44. VallienG, LangleyR, JenningsS, SpecianR, GrangerD (2000) Expression of endothelial cell adhesion molecules in neovascularized tissue. Microcirculation 7: 249–258.
45. McDonaldB, McAvoyEF, LamF, GillV, delM, et al. (2008) Interaction of CD44 and hyaluronan is the dominant mechanism for neutrophil sequestration in inflamed liver sinusoids. J Exp Med 205: 915–927.
46. YippBG, PetriB, SalinaD, JenneCN, ScottBN, et al. (2012) Infection-induced NETosis is a dynamic process involving neutrophil multitasking in vivo. Nat Med 18: 1386–1393.
47. CashHA, WoodsDE, McCulloughB, JohansonWGJ, BassJA (1979) A rat model of chronic respiratory infection with Pseudomonas aeruginosa. Am Rev Respir Dis 3: 453–459.
48. YippBG, KubesP (2013) Antibodies against neutrophil LY6G do not inhibit leukocyte recruitment in mice in vivo. Blood 121: 241–242 10.1182/blood-2012-09-454348.
49. HwangJM, YamanouchiJ, SantamariaP, KubesP (2004) A critical temporal window for selectin-dependent CD4+ lymphocyte homing and initiation of late-phase inflammation in contact sensitivity. J Exp Med 199: 1223–1234.
Štítky
Hygiena a epidemiológia Infekčné lekárstvo LaboratóriumČlánok vyšiel v časopise
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