Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Chronic bacterial infections: living with unwanted guests

Abstract

Some bacterial pathogens can establish life-long chronic infections in their hosts. Persistence is normally established after an acute infection period involving activation of both the innate and acquired immune systems. Bacteria have evolved specific pathogenic mechanisms and harbor sets of genes that contribute to the establishment of a persistent lifestyle that leads to chronic infection. Persistent bacterial infection may involve occupation of a particular tissue type or organ or modification of the intracellular environment within eukaryotic cells. Bacteria appear to adapt their immediate environment to favor survival and may hijack essential immunoregulatory mechanisms designed to minimize immune pathology or the inappropriate activation of immune effectors.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Schematic representation of a model for persistence in human typhoid involving S. enterica Typhi.
Figure 2: Persistent infection with M. tuberculosis.

References

  1. Hijjar, A.M., Ernst, R.K., Tsai, J.H., Wilson, C.B. & Miller, S.I. Human Toll-like receptor 4 recognizes host-specific LPS modifications. Nature Immunol. 3, 354–359 (2002).

    Google Scholar 

  2. Guo, L. et al. Regulation of lipid A modifications by Salmonella typhimurium virulence genes phoP-phoQ. Science 276, 250–253 (1997).

    CAS  PubMed  Google Scholar 

  3. Stockinger, B., Barthlott, T. & Kassiotis, G. T cell regulation: a special job or everyone's responsibility? Nature Immunol. 2, 757–758 (2001).

    CAS  Google Scholar 

  4. Krinos, C.M., Coyne, M.J., Weinacht, K.G., Tzianabos, A.O., Kasper, D.L. & Comstock, L.E. Extensive surface diversity of a commensal microorganism by multiple DNA inversions. Nature 414, 555–558 (2001).

    CAS  PubMed  Google Scholar 

  5. Virji, M., Makepeace, K., Peak, I.R., Ferguson, D.J. & Moxon, E.R. Pathogenic mechanisms of Neisseria meningitides. Ann. NY Acad. Sci. 797, 273–276 (1996).

    CAS  PubMed  Google Scholar 

  6. Ma, A., Datta, M., Margosian, E., Chen, J. & Horak, I. T cells, but not B cells, are required for bowel inflammation in interleukin 2-deficient mice. J. Exp. Med. 182, 1567–1572 (1995).

    CAS  PubMed  Google Scholar 

  7. Kuhn, R., Lohler, J., Rennick, D., Rajewsky, K. & Muller, W. Interleukin-10-deficient mice develop chronic enterocolitis. Cell 75, 263–274 (1993).

    CAS  PubMed  Google Scholar 

  8. Sellon, R.K. et al. Resident enteric bacteria are necessary for development of spontaneous colitis and immune system activation in interleukin-10-deficient mice. Infect. Immun. 66, 5224–5231 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Simpson, S.J. et al. T cell-mediated pathology in two models of experimental colitis depends predominantly on the interleukin 12/signal transducer and activator of transcription (Stat)-4 pathway, but is not conditional on interferon γ expression by T cells. J. Exp. Med. 187, 1225–1234 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Takeda, K. et al. Enhanced Th1 activity and development of chronic enterocolitis in mice devoid of Stat3 in macrophages and neutrophils. Immunity 10, 39–49 (1999).

    CAS  PubMed  Google Scholar 

  11. Strober, W., Nakamura, K. & Kitani, A. The SAMP1/Yit mouse: another step closer to modeling human inflammatory bowel disease. J. Clin. Invest. 107, 667–670 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Panwala, C.M., Jones, J.C. & Viney, J.L. A novel model of inflammatory bowel disease: mice deficient for the multiple drug resistance gene, mdr1a, spontaneously develop colitis. J. Immunol. 161, 5733–5744 (1998).

    CAS  PubMed  Google Scholar 

  13. Hermiston, M.L. & Gordon, J.I. Inflammatory bowel disease and adenomas in mice expressing a dominant negative N-cadherin. Science 270, 1203–1207 (1995).

    CAS  PubMed  Google Scholar 

  14. Madsen, K.L. et al. Antibiotic therapy attenuates colitis in interleukin 10 gene-deficient mice. Gastroenterology 118, 1094–1105 (2000).

    CAS  PubMed  Google Scholar 

  15. Nagler-Anderson, C. Man the barrier! Strategic defences in the intestinal mucosa. Nature Rev. Immunol. 1, 59–67 (2001).

    CAS  Google Scholar 

  16. Strobel, S. & Mowat, A.M. Immune responses to dietary antigens: oral tolerance. Immunol. Today 19, 173–181 (1998).

    CAS  PubMed  Google Scholar 

  17. Macpherson, A.J. et al. IgA production without μ or δ chain expression in developing B cells. Nature Immunol. 2, 625–631 (2001).

    CAS  Google Scholar 

  18. Hooper, L.V. & Gordon, J.I. Commensal host-bacterial relationships in the gut. Science 292, 1115–1118 (2001).

    CAS  PubMed  Google Scholar 

  19. Cario, E. & Podolsky, D.K. Differential alteration in intestinal epithelial cell expression of toll-like receptor 3 (TLR3) and TLR4 in inflammatory bowel disease. Infect. Immun. 68, 7010–7017 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Smith, P.D. et al. Intestinal macrophages lack CD14 and CD89 and consequently are down–regulated for LPS- and IgA-mediated activities. J. Immunol. 167, 2651–2656 (2001).

    CAS  PubMed  Google Scholar 

  21. Blumberg, R.S., Saubermann, L.J. & Strober, W. Animal models of mucosal inflammation and their relation to human inflammatory bowel disease. Curr. Opin. Immunol. 11, 648–656 (1999).

    CAS  PubMed  Google Scholar 

  22. Groux, H. et al. A CD4+ T-cell subset inhibits antigen-specific T-cell responses and prevents colitis. Nature 389, 737–742 (1997).

    CAS  PubMed  Google Scholar 

  23. Newberry, R.D., McDonough, J.S., Stenson, W.F. & Lorenz, R.G. Spontaneous and continuous cyclooxygenase-2-dependent prostaglandin E2 production by stromal cells in the murine small intestine lamina propria: directing the tone of the intestinal immune response. J. Immunol. 166, 4465–4472 (2001).

    CAS  PubMed  Google Scholar 

  24. Maloy, K.J. & Powrie, F. Regulatory T cells in the control of immune pathology. Nature Immunol. 2, 816–822 (2001).

    CAS  Google Scholar 

  25. Zabel, B.A. et al. Human G protein-coupled receptor GPR-9-6/CC chemokine receptor 9 is selectively expressed on intestinal homing T lymphocytes, mucosal lymphocytes, and thymocytes and is required for thymus-expressed chemokine-mediated chemotaxis. J. Exp. Med. 190, 1241–1256 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Rappuoli, R., Pizza, M., Douce, G. & Dougan, G. Structure and mucosal adjuvanticity of cholera and Escherichia coli heat-labile enterotoxins. Immunol. Today 20, 493–500 (1999).

    CAS  PubMed  Google Scholar 

  27. Macdonald, T.T. & Monteleone, G. IL-12 and Th1 immune responses in human Peyer's patches. Trends. Immunol 22, 244–247 (2001).

    CAS  PubMed  Google Scholar 

  28. Wain, J. et al. Molecular typing of multiple-antibiotic-resistant Salmonella enterica serovar Typhi from Vietnam: application to acute and relapse cases of typhoid fever. J. Clin. Microbiol. 37, 2466–2472 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Wain, J. et al. Quantitation of bacteria in bone marrow from patients with typhoid fever: relationship between counts and clinical features. J. Clin. Microbiol. 39, 1571–1576 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Parkhill, J. et al. genome sequence of a multiple drug resistant Salmonella enterica serovar Typhi CT18. Nature 413, 848–852 (2001).

    CAS  PubMed  Google Scholar 

  31. McClelland, M. et al. Complete genome sequence of Salmonella enterica serovar Typhimurium LT2. Nature 413, 852–856 (2001).

    CAS  PubMed  Google Scholar 

  32. Townsend, S.M. et al. Salmonella enterica serovar Typhi possesses a unique repertoire of fimbrial gene sequences. Infect. Immun. 69, 2894–2901 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Kingsley, R.A., Santos, R.L.K.A.M., Adams, L.G. & Baumler, A.J. Salmonella enteritica serotype Typhimurium ShdA is an outer membrane fibronectin-binding protein that is expressed in the intestine. Mol. Microbiol. 43, 895–905 (2002).

    CAS  PubMed  Google Scholar 

  34. Hughes, E.A. & Galan, J.E. Immune response to Salmonella: location, location, location? Immunity 16, 325–328 (2002).

    CAS  PubMed  Google Scholar 

  35. Parkhill, J. et al. Genome sequence of Yersinia pestis, the causative agent of plague. Nature 413, 523–527 (2001).

    CAS  PubMed  Google Scholar 

  36. Cole, S.T. et al. Massive gene decay in the leprosy bacillus. Nature 409, 1007–1011 (2001).

    CAS  PubMed  Google Scholar 

  37. Rescigno, M. et al. Dendritic cells express tight junction proteins and penetrate gut epithelial monolayers to sample bacteria. Nature Immunol. 2, 361–367 (2001).

    CAS  Google Scholar 

  38. Vazquez-Torres, A. et al. Extraintestinal dissemination of Salmonella by CD18-expressing phagocytes. Nature 401, 804–808 (1999).

    CAS  PubMed  Google Scholar 

  39. Hindle, Z. et al. Characterisation in volunteers of Salmonella enteritica derivatives harboring defined aroC and SPI-2 type III secretion system (ssaV) mutations. Infect. Immun. 70, 3457–3467 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Clements, M.O. et al. Polynucleotide phosphorylase is a global regulator of virulence and persistency in Salmonella enterica. Proc. Natl. Acad. Sci. USA 99, 8784–8789 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  41. O'Callaghan, D., Maskell, D., Liew, F.Y., Easmon, C.S. & Dougan, G. Characterization of aromatic- and purine-dependent Salmonella typhimurium: attention, persistence, and ability to induce protective immunity in BALB/c mice. Infect. Immun. 56, 419–423 (1988).

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Warren, J. et al. Increased susceptibility of C1q-deficient mice to Salmonella enterica serovar Typhimurium infection. Infect. Immun. 70, 551–557 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Mastroeni, P., Simmons, C., Fowler, R., Hormaeche, C.E. & Dougan, G. Igh-6−/− (B-cell-deficient) mice fail to mount solid acquired resistance to oral challenge with virulent Salmonella enterica serovar typhimurium and show impaired Th1 T-cell responses to Salmonella antigens. Infect. Immun. 68, 46–53 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Salcedo, S.P., Noursadeghi, M., Cohen, J. & Holden, D.W. Intracellular replication of Salmonella typhimurium strains in specific subsets of splenic macrophages in vivo. Cell Microbiol. 3, 587–597 (2001).

    CAS  PubMed  Google Scholar 

  45. Dunstan, S.J. et al. fever and genetic polymorphisms at the natural resistance-associated macrophage protein 1. J. Infect. Dis. 183, 1156–1160 (2001).

    CAS  PubMed  Google Scholar 

  46. Hess, J., Ladel, C., Miko, D. & Kaufmann, S.H. Salmonella typhimurium aroA- infection in gene-targeted immunodeficient mice: major role of CD4+ TCR-αβ cells and IFN-γ in bacterial clearance independent of intracellular location. J. Immunol. 156, 3321–3326 (1996).

    CAS  PubMed  Google Scholar 

  47. Nauciel, C. Role of CD4+ T cells and T-independent mechanisms in acquired resistance to Salmonella typhimurium infection. J. Immunol. 145, 1265–1269 (1990).

    CAS  PubMed  Google Scholar 

  48. O'Brien, A.D. & Metcalf, E.S. Control of early Salmonella typhimurium growth in innately Salmonella-resistant mice does not require functional T lymphocytes. J. Immunol. 129, 1349–1351 (1982).

    CAS  PubMed  Google Scholar 

  49. Mittrucker, H.W., Kohler, A., Mak, T.W. & Kaufmann, S.H. Critical role of CD28 in protective immunity against Salmonella typhimurium. J. Immunol. 163, 6769–6776 (1999).

    CAS  PubMed  Google Scholar 

  50. McSorley, S.J. & Jenkins, M.K. Antibody is required for protection against virulent but not attenuated Salmonella enterica serovar typhimurium. Infect. Immun. 68, 3344–3348 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Dunstan, S.J. et al. Genes of the class II and class III major histocompatibility complex are associated with typhoid fever in Vietnam. J. Infect. Dis. 183, 261–268 (2001).

    CAS  PubMed  Google Scholar 

  52. Russell, D.G. Mycobacterium tuberculosis: here today, and here tomorrow. Nature Rev. Mol. Cell Biol. 2, 569–577 (2001).

    CAS  Google Scholar 

  53. Brennan, P.J. & Nikaido, H. The envelope of mycobacteria. Annu. Rev. Biochem. 64, 29–63 (1995).

    CAS  PubMed  Google Scholar 

  54. Cole, S.T. et al. Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature 393, 537–544 (1998).

    CAS  PubMed  Google Scholar 

  55. Barry, C.E. Interpreting cell wall 'virulence factors' of Mycobacterium tuberculosis. Trends. Microbiol. 9, 237–241 (2001).

    CAS  PubMed  Google Scholar 

  56. Bryk, R., Lima, C.D., Erdjument-Bromage, H., Tempst, P. & Nathan, C. Metabolic enzymes of mycobacteria linked to antioxidant defense by a thioredoxin-like protein. Science 295, 1073–1077 (2002).

    CAS  PubMed  Google Scholar 

  57. Hondalus, M.K. et al. Attenuation of and protection induced by a leucine auxotroph of Mycobacterium tuberculosis. Infect. Immun. 68, 2888–2898 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Via, L.E. et al. Effects of cytokines on mycobacterial phagosome maturation. J. Cell Sci. 111, 897–905 (1998).

    CAS  PubMed  Google Scholar 

  59. Casanova, J.L. & Abel, L. Genetic dissection of immunity to mycobacteria: the human model. Annu. Rev. Immunol. 20, 581–620 (2002).

    CAS  PubMed  Google Scholar 

  60. Flynn, J.L. & Chan, J. Immunology of tuberculosis. Annu. Rev. Immunol. 19, 93–129 (1902).

    Google Scholar 

  61. Brightbill, H.D. et al. Host defense mechanisms triggered by microbial lipoproteins through toll-like receptors. Science 285, 732–736 (1999).

    CAS  PubMed  Google Scholar 

  62. Underhill, D.M., Ozinsky, A., Smith, K.D. & Aderem, A. Toll-like receptor-2 mediates mycobacteria-induced proinflammatory signaling in macrophages. Proc. Natl. Acad. Sci. USA 96, 14459–14463 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Nau, G.J. et al. Human macrophage activation programs induced by bacterial pathogens. Proc. Natl. Acad. Sci. USA 99, 1503–1508 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  64. Constant, P. et al. Stimulation of human γδ T cells by nonpeptidic mycobacterial ligands. Science 264, 267–270 (1994).

    CAS  PubMed  Google Scholar 

  65. Ulrichs, T. & Porcelli, S.A. CD1 proteins: targets of T cell recognition in innate and adaptive immunity. Rev. Immunogenet. 2, 416–432 (2000).

    CAS  PubMed  Google Scholar 

  66. Schaible, U.E., Hagens, K., Fischer, K., Collins, H.L. & Kaufmann, S.H. Intersection of group I CD1 molecules and mycobacteria in different intracellular compartments of dendritic cells. J. Immunol. 164, 4843–4852 (2000).

    CAS  PubMed  Google Scholar 

  67. Neyrolles, O. et al. Lipoprotein access to MHC class I presentation during infection of murine macrophages with live mycobacteria. J. Immunol. 166, 447–457 (2001).

    CAS  PubMed  Google Scholar 

  68. Stenger, S. et al. Differential effects of cytolytic T cell subsets on intracellular infection. Science 276, 1684–1687 (1997).

    CAS  PubMed  Google Scholar 

  69. Noss, E.H. et al. Toll-like receptor 2-dependent inhibition of macrophage class II MHC expression and antigen processing by 19-kDa lipoprotein of Mycobacterium tuberculosis. J. Immunol. 167, 910–918 (2001).

    CAS  PubMed  Google Scholar 

  70. Seah, G.T., Scott, G.M. & Rook, G.A. Type 2 cytokine gene activation and its relationship to extent of disease in patients with tuberculosis. J. Infect. Dis. 181, 385–389 (2000).

    CAS  PubMed  Google Scholar 

  71. Ting, L.M., Kim, A.C., Cattamanchi, A. & Ernst, J.D. Mycobacterium tuberculosis inhibits IFN-γ transcriptional responses without inhibiting activation of STAT1. J. Immunol. 163, 3898–3906 (1999).

    CAS  PubMed  Google Scholar 

  72. Rich, A.R. The Pathogenesis of Tuberculosis (Blackwell Scientific Publications, Oxford, 2002).

    Google Scholar 

  73. Opie, E.L. & Aronson, J.D. Tubercle bacilli in latent tuberculosis lesions and in lung tissue without tuberculosis lesions. Arch. Pathol. 4, 1–21 (1927).

    Google Scholar 

  74. Hernandez-Pando, R. et al. Persistence of DNA from Mycobacterium tuberculosis in superficially normal lung tissue during latent infection. Lancet 356, 2133–2138 (2000).

    CAS  PubMed  Google Scholar 

  75. Vandiviere, H.M., Loring, W.E., Melvin, I. & Willis, S. The treated pulmonary lesion and its tubercule bacillus. II The death and the resurrection. Am. J. Med. Sci. 232, 30–37 (1956).

    CAS  PubMed  Google Scholar 

  76. Rees, R.J. & Hart, P.D. Analysis of the host-parasite equilibrium in chronic murine tuberculosis by total and viable bacillary counts. Br. J. Exp. Pathol. 42, 83–88 (1961).

    CAS  PubMed  PubMed Central  Google Scholar 

  77. Wallace, J.G. The heat resistance of tubercule in the lungs of infected mice. Am. Rev. Respir. Dis. 83, 866–871 (1961).

    CAS  PubMed  Google Scholar 

  78. McKinney, J.D. et al. Persistence of Mycobacterium tuberculosis in macrophages and mice requires the glyoxylate shunt enzyme isocitrate lyase. Nature 406, 735–738 (2000).

    CAS  PubMed  Google Scholar 

  79. Stewart, G.R. et al. Overexpression of heat-shock proteins reduces survival of Mycobacterium tuberculosis in the chronic phase of infection. Nature Med. 7, 732–737 (2001).

    CAS  PubMed  Google Scholar 

  80. Perez, E. et al. An essential role for phoP in Mycobacterium tuberculosis virulence. Mol. Microbiol. 41, 179–187 (2001).

    CAS  PubMed  Google Scholar 

  81. McCune, R.M., Feldmann, F.M., Lambert, H.P. & McDermott, W. Microbial persistence. I. The capacity of tubercle bacilli to survive sterilization in mouse tissues. J. Exp. Med. 123, 445–468 (1966).

    CAS  PubMed  PubMed Central  Google Scholar 

  82. Wayne, L.G. & Sohaskey, C.D. Nonreplicating persistence of Mycobacterium tuberculosis. Annu. Rev. Microbiol. 55, 139–163 (1902).

    Google Scholar 

  83. Sherman, D.R. et al. Regulation of the Mycobacterium tuberculosis hypoxic response gene encoding α-crystallin. Proc. Natl. Acad. Sci. USA 98, 7534–7539 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  84. Keane, J. et al. Tuberculosis associated with infliximab, a tumor necrosis factor α-neutralizing agent. N. Engl. J. Med. 345, 1098–1104 (2001).

    CAS  PubMed  Google Scholar 

  85. Moreira, A.L. et al. Mycobacterial antigens exacerbate disease manifestations in Mycobacterium tuberculosis-infected mice. Infect. Immun. 70, 2100–2107 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  86. O'Callaghan, D. et al. A homologue of the Agrobacterium tumefaciens VirB and Bordetella pertussis Ptl type IV secretion systems is essential for intracellular survival of Brucella suis. Mol. Microbiol. 33, 1210–1220 (1999).

    CAS  PubMed  Google Scholar 

  87. Boschiroli, M.L. et al. The Brucella suis virB operon is induced intracellularly in macrophages. Proc. Natl. Acad. Sci. USA 99, 1544–1549 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  88. Boulton, I.C. & Gray-Owen, S.D. Neisserial binding to CEACAM1 arrests the activation and proliferation of CD4+ T lymphocytes. Nature Immunol. 3, 229–236 (2002).

    CAS  Google Scholar 

  89. Byrne, G.I. et al. Chlamydia pneumoniae expresses genes required for DNA replication but not cytokinesis during persistent infection of HEp-2 cells. Infect. Immun. 69, 5423–5429 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  90. Fischer, S.F., Schwarz, C., Vier, J. & Hacker, G. Characterization of antiapoptotic activities of Chlamydia pneumoniae in human cells. Infect. Immun. 69, 7121–7129 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  91. Fraser, C.M. et al. Genomic sequence of a Lyme disease spirochaete, Borrelia burgdorferi. Nature 390, 580–586 (1997).

    CAS  PubMed  Google Scholar 

  92. Merz, A.J. & So, M. Interactions of pathogenic neisseriae with epithelial cell membranes. Annu. Rev. Cell Dev. Biol. 16, 423–457 (2000).

    CAS  PubMed  Google Scholar 

  93. Brennan, M.J. & Delogu, G. The PE multigene family: a 'molecular mantra' for mycobacteria. Trends. Microbiol. 10, 246–249 (2002).

    CAS  PubMed  Google Scholar 

  94. Porcella, S.F. & Schwan, T.G. Borrelia burgdorferi and Treponema pallidum: a comparison of functional genomics, environmental adaptations, and pathogenic mechanisms. J. Clin. Invest. 107, 651–656 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  95. Sansonetti, P. Phagocytosis of bacterial pathogens: implications in the host response. Semin. Immunol. 13, 381–390 (2001).

    CAS  PubMed  Google Scholar 

  96. Galyov, E.E. et al. A secreted effector protein of Salmonella dublin is translocated into eukaryotic cells and mediates inflammation and fluid secretion in infected ileal mucosa. Mol. Microbiol. 25, 903–912 (1997).

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

Supported by The Wellcome Trust (G. D. and D. Y.) and the Medical Research Council (T. H.).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Gordon Dougan.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Young, D., Hussell, T. & Dougan, G. Chronic bacterial infections: living with unwanted guests. Nat Immunol 3, 1026–1032 (2002). https://doi.org/10.1038/ni1102-1026

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/ni1102-1026

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing