Independent Bottlenecks Characterize Colonization of Systemic Compartments and Gut Lymphoid Tissue by
Pathogens have evolved strategies to invade, replicate and spread within their hosts. On the contrary, vertebrates have developed sophisticated immune defence mechanisms that limit, and ideally clear, the infection. This dynamic interplay between host and pathogens determines the course of the infection and the development of clinical disease. Knowledge on particularly vulnerable steps in the infection process, i.e. the “Achilles heel” of a pathogen, may guide the development of anti-infective therapies and vaccines. However, for most pathogens we lack detailed information on the dynamics of the infection process. Here we determined bottlenecks, i.e. critical steps during pathogen invasion and spread, after oral Salmonella infection in non-manipulated and vaccinated mice. We infected mice with mixtures of tagged Salmonella strains and analysed the strain composition in different compartments by high throughput sequencing. This information allowed us to estimate the number of Salmonella invading a given tissue and to describe routes of pathogen dissemination. We show that vaccination only modestly reduces invasion of intestinal lymphoid tissue but had a profound effect on the spread of Salmonella to systemic compartments.
Vyšlo v časopise:
Independent Bottlenecks Characterize Colonization of Systemic Compartments and Gut Lymphoid Tissue by. PLoS Pathog 10(7): e32767. doi:10.1371/journal.ppat.1004270
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.ppat.1004270
Souhrn
Pathogens have evolved strategies to invade, replicate and spread within their hosts. On the contrary, vertebrates have developed sophisticated immune defence mechanisms that limit, and ideally clear, the infection. This dynamic interplay between host and pathogens determines the course of the infection and the development of clinical disease. Knowledge on particularly vulnerable steps in the infection process, i.e. the “Achilles heel” of a pathogen, may guide the development of anti-infective therapies and vaccines. However, for most pathogens we lack detailed information on the dynamics of the infection process. Here we determined bottlenecks, i.e. critical steps during pathogen invasion and spread, after oral Salmonella infection in non-manipulated and vaccinated mice. We infected mice with mixtures of tagged Salmonella strains and analysed the strain composition in different compartments by high throughput sequencing. This information allowed us to estimate the number of Salmonella invading a given tissue and to describe routes of pathogen dissemination. We show that vaccination only modestly reduces invasion of intestinal lymphoid tissue but had a profound effect on the spread of Salmonella to systemic compartments.
Zdroje
1. CrumpJA, LubySP, MintzED (2004) The global burden of typhoid fever. Bull World Health Organ 82: 346–353.
2. MacLennanCA, GilchristJJ, GordonMA, CunninghamAF, CobboldM, et al. (2010) Dysregulated humoral immunity to nontyphoidal Salmonella in HIV-infected African adults. Science 328: 508–512.
3. BhanMK, BahlR, BhatnagarS (2005) Typhoid and paratyphoid fever. Lancet 366: 749–762.
4. JohnsonKJ (2012) Crossing borders: one world, global health: CDC updates recommendations for typhoid vaccination. Clin Infect Dis 54: v–vi.
5. PabstO (2012) New concepts in the generation and functions of IgA. Nat Rev Immunol 12: 821–832.
6. MichettiP, MahanMJ, SlauchJM, MekalanosJJ, NeutraMR (1992) Monoclonal secretory immunoglobulin A protects mice against oral challenge with the invasive pathogen Salmonella typhimurium. Infect Immun 60: 1786–1792.
7. MartinoliC, ChiavelliA, RescignoM (2007) Entry route of Salmonella typhimurium directs the type of induced immune response. Immunity 27: 975–984.
8. UrenTK, WijburgOL, SimmonsC, JohansenFE, BrandtzaegP, et al. (2005) Vaccine-induced protection against gastrointestinal bacterial infections in the absence of secretory antibodies. Eur J Immunol 35: 180–188.
9. NantonMR, WaySS, ShlomchikMJ, McSorleySJ (2012) Cutting edge: B cells are essential for protective immunity against Salmonella independent of antibody secretion. J Immunol 189: 5503–5507.
10. LevineMM, TacketCO, SzteinMB (2001) Host-Salmonella interaction: human trials. Microbes Infect 3: 1271–1279.
11. MaiNL, PhanVB, VoAH, TranCT, LinFY, et al. (2003) Persistent efficacy of Vi conjugate vaccine against typhoid fever in young children. N Engl J Med 349: 1390–1391.
12. MacLennanCA, GondweEN, MsefulaCL, KingsleyRA, ThomsonNR, et al. (2008) The neglected role of antibody in protection against bacteremia caused by nontyphoidal strains of Salmonella in African children. J Clin Invest 118: 1553–1562.
13. CrimminsGT, IsbergRR (2012) Analyzing microbial disease at high resolution: following the fate of the bacterium during infection. Curr Opin Microbiol 15: 23–27.
14. MastroeniP, GrantAJ (2011) Spread of Salmonella enterica in the body during systemic infection: unravelling host and pathogen determinants. Expert Rev Mol Med 13: e12.
15. BarnesPD, BergmanMA, MecsasJ, IsbergRR (2006) Yersinia pseudotuberculosis disseminates directly from a replicating bacterial pool in the intestine. J Exp Med 203: 1591–1601.
16. GrantAJ, FosterGL, McKinleyTJ, BrownSP, ClareS, et al. (2009) Bacterial growth rate and host factors as determinants of intracellular bacterial distributions in systemic Salmonella enterica infections. Infect Immun 77: 5608–5611.
17. GrantAJ, RestifO, McKinleyTJ, SheppardM, MaskellDJ, et al. (2008) Modelling within-host spatiotemporal dynamics of invasive bacterial disease. PLoS Biol 6: e74.
18. KaiserP, SlackE, GrantAJ, HardtWD, RegoesRR (2013) Lymph node colonization dynamics after oral salmonella typhimurium infection in mice. PLoS Pathog 9: e1003532.
19. ZhangX, FletcherSA, CsonkaLN (1996) Site-directed mutational analysis of the osmotically regulated proU promoter of Salmonella typhimurium. J Bacteriol 178: 3377–3379.
20. ValdezY, FerreiraRB, FinlayBB (2009) Molecular mechanisms of Salmonella virulence and host resistance. Curr Top Microbiol Immunol 337: 93–127.
21. HaseK, KawanoK, NochiT, PontesGS, FukudaS, et al. (2009) Uptake through glycoprotein 2 of FimH(+) bacteria by M cells initiates mucosal immune response. Nature 462: 226–230.
22. VoedischS, KoeneckeC, DavidS, HerbrandH, ForsterR, et al. (2009) Mesenteric lymph nodes confine dendritic cell-mediated dissemination of Salmonella enterica serovar Typhimurium and limit systemic disease in mice. Infect Immun 77: 3170–3180.
23. MantisNJ, RolN, CorthesyB (2011) Secretory IgA's complex roles in immunity and mucosal homeostasis in the gut. Mucosal Immunol 4: 603–611.
24. WatsonKG, HoldenDW (2010) Dynamics of growth and dissemination of Salmonella in vivo. Cell Microbiol 12: 1389–1397.
25. OellerichMF, JacobiCA, FreundS, NiedungK, BachA, et al. (2007) Yersinia enterocolitica infection of mice reveals clonal invasion and abscess formation. Infect Immun 75: 3802–3811.
26. SheppardM, WebbC, HeathF, MallowsV, EmilianusR, et al. (2003) Dynamics of bacterial growth and distribution within the liver during Salmonella infection. Cell Microbiol 5: 593–600.
27. MeynellGG, StockerBA (1957) Some hypotheses on the aetiology of fatal infections in partially resistant hosts and their application to mice challenged with Salmonella paratyphi-B or Salmonella typhimurium by intraperitoneal injection. J Gen Microbiol 16: 38–58.
28. HelaineS, ThompsonJA, WatsonKG, LiuM, BoyleC, et al. (2010) Dynamics of intracellular bacterial replication at the single cell level. Proc Natl Acad Sci U S A 107: 3746–3751.
29. MacphersonAJ, UhrT (2004) Induction of protective IgA by intestinal dendritic cells carrying commensal bacteria. Science 303: 1662–1665.
30. WijburgOL, UrenTK, SimpfendorferK, JohansenFE, BrandtzaegP, et al. (2006) Innate secretory antibodies protect against natural Salmonella typhimurium infection. J Exp Med 203: 21–26.
31. RollenhagenC, BumannD (2006) Salmonella enterica highly expressed genes are disease specific. Infect Immun 74: 1649–1660.
32. DatsenkoKA, WannerBL (2000) One-step inactivation of chromosomal genes in Escherichia coli K-12 using PCR products. Proc Natl Acad Sci U S A 97: 6640–6645.
33. HochwellerK, StrieglerJ, HammerlingGJ, GarbiN (2008) A novel CD11c.DTR transgenic mouse for depletion of dendritic cells reveals their requirement for homeostatic proliferation of natural killer cells. Eur J Immunol 38: 2776–2783.
Štítky
Hygiena a epidemiológia Infekčné lekárstvo LaboratóriumČlánok vyšiel v časopise
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