Skip to main content

Advertisement

SpringerLink
Log in

Impact of lymphocyte apoptosis on the innate immune stages of infection

  • Published:
Immunologic Research Aims and scope Submit manuscript

Abstract

Infection of mice with Listeria monocytogenes has led to a puzzling observation: mice deficient in lymphocytes are more resistant during the early innate immune response. This is counterintuitive, because mice deficient in the adaptive immune response are unable to clear the infection and eventually die. This work will highlight some of our recent work on Listeria induced apoptosis and its immunological consequences. We show that Listeria produces a toxin, listeriolysin O (LLO), which causes apoptosis of lymphocytes in vitro and in vivo. Early during the infection, type I interferon sensitizes lymphocytes to die by LLO-induced apoptosis. The cell death peaks during the first two days of the infection, leading to the production of IL-10 and downregulation of anti-microbial activity in the spleen. The induction of apoptosis by Listeria creates an infective niche in the peri-arteriolar lymphoid sheaths of the spleen which allows the bacteria to grow exponentially.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

References

  1. Merrick JC, Edelson BT, Bhardwaj V, Swanson PE, Unanue ER. Lymphocyte apoptosis during early phase of Listeria infection in mice. Am J Pathol 1997;151:785–92

    PubMed  CAS  Google Scholar 

  2. Edelson BT, Cossart P, Unanue ER. Cutting edge: paradigm revisited: antibody provides resistance to Listeria infection. J Immunol 1999;163:4087–90

    PubMed  CAS  Google Scholar 

  3. Carrero JA, Calderon B, Unanue ER. Listeriolysin O from Listeria monocytogenes is a lymphocyte apoptogenic molecule. J Immunol 2004;172:4866–74

    PubMed  CAS  Google Scholar 

  4. Carrero JA, Calderon B, Unanue ER. Type I interferon sensitizes lymphocytes to apoptosis and reduces resistance to Listeria infection. J Exp Med 2004;200:535–40

    Article  PubMed  CAS  Google Scholar 

  5. Carrero JA, Calderon B, Unanue ER. Lymphocytes are detrimental during the early innate immune response against Listeria monocytogenes. J Exp Med 2006;203:933–40

    Article  PubMed  CAS  Google Scholar 

  6. Emmerling P, Finger H, Bockemuhl J. Listeria monocytogenes infection in nude mice. Infect Immun 1975;12:437–39

    PubMed  CAS  Google Scholar 

  7. Skamene E, Chayasirisobhon W. Enhanced resistance to Listeria monocytogenes in splenectomized mice. Immunology 1977;33:851–58

    PubMed  CAS  Google Scholar 

  8. Bancroft GJ, Bosma MJ, Bosma GC, Unanue ER. Regulation of macrophage Ia expression in mice with severe combined immunodeficiency: induction of Ia expression by a T cell-independent mechanism. J Immunol 1986;137:4–9

    PubMed  CAS  Google Scholar 

  9. Ochsenbein AF, Fehr T, Lutz C, Suter M, Brombacher F, Hengartner H, Zinkernagel RM. Control of early viral and bacterial distribution and disease by natural antibodies. Science 1999;286:2156–59

    Article  PubMed  CAS  Google Scholar 

  10. Bhardwaj V, Kanagawa O, Swanson PE, Unanue ER. Chronic Listeria infection in SCID mice: requirements for the carrier state and the dual role of T cells in transferring protection or suppression. J Immunol 1998;160:376–84

    PubMed  CAS  Google Scholar 

  11. Muraille E, Giannino R, Guirnalda P, Leiner I, Jung S, Pamer EG, Lauvau G. Distinct in vivo dendritic cell activation by live versus killed Listeria monocytogenes. Eur J Immunol 2005;35:1463–71

    Article  PubMed  CAS  Google Scholar 

  12. Edelson BT, Unanue ER. Intracellular antibody neutralizes Listeria growth. Immunity 2001;14:503–12

    Article  PubMed  CAS  Google Scholar 

  13. Portnoy DA, Auerbuch V, Glomski IJ. The cell biology of Listeria monocytogenes infection: the intersection of bacterial pathogenesis and cell-mediated immunity. J Cell Biol 2002;158:409–14

    Article  PubMed  CAS  Google Scholar 

  14. Auerbuch V, Brockstedt DG, Meyer-Morse N, O’Riordan M, Portnoy DA. Mice lacking the type I interferon receptor are resistant to Listeria monocytogenes. J Exp Med 2004;200:527–33

    Article  PubMed  CAS  Google Scholar 

  15. O’Connell RM, Saha SK, Vaidya SA, Bruhn KW, Miranda GA, Zarnegar B, Perry AK, Nguyen BO, Lane TF, Taniguchi T, Miller JF, Cheng G. Type I interferon production enhances susceptibility to Listeria monocytogenes infection. J Exp Med 2004;200:437–45

    Article  PubMed  CAS  Google Scholar 

  16. Theofilopoulos AN, Baccala R, Beutler B, Kono DH. Type I interferons (alpha/beta) in immunity and autoimmunity. Annu Rev Immunol 2005;23:307–36

    Article  PubMed  CAS  Google Scholar 

  17. Takaoka A, Hayakawa S, Yanai H, Stoiber D, Negishi H, Kikuchi H, Sasaki S, Imai K, Shibue T, Honda K, Taniguchi T. Integration of interferon-alpha/beta signalling to p53 responses in tumour suppression and antiviral defence. Nature 2003;424:516–23

    Article  PubMed  CAS  Google Scholar 

  18. Voll RE, Herrmann M, Roth EA, Stach C, Kalden JR, Girkontaite I. Immunosuppressive effects of apoptotic cells. Nature 1997;390:350–51

    Article  PubMed  CAS  Google Scholar 

  19. Savill J, Fadok V. Corpse clearance defines the meaning of cell death. Nature 2000;407:784–88

    Article  PubMed  CAS  Google Scholar 

  20. Savill J, Dransfield I, Gregory C, Haslett C. A blast from the past: clearance of apoptotic cells regulates immune responses. Nature Reviews Immunology 2002;2:965–75

    Article  PubMed  CAS  Google Scholar 

  21. Dai WJ, Kohler G, Brombacher F. Both innate and acquired immunity to Listeria monocytogenes infection are increased in IL-10-deficient mice. J Immunol 1997;158:2259–67

    PubMed  CAS  Google Scholar 

  22. Carrero JA, Unanue ER. Lymphocyte apoptosis as an immune subversion strategy of microbial pathogens. Trends Immunol 2006;27:497–503

    Article  PubMed  CAS  Google Scholar 

  23. O’Riordan M, Yi CH, Gonzales R, Lee KD, Portnoy DA. Innate recognition of bacteria by a macrophage cytosolic surveillance pathway. Proc Natl Acad Sci U S A 2002;99:13861–6

    Article  PubMed  CAS  Google Scholar 

  24. Winau F, Hegasy G, Kaufmann SH, Schaible UE. No life without death-apoptosis as prerequisite for T cell activation. Apoptosis 2005;10:707–15

    Article  PubMed  CAS  Google Scholar 

  25. Winau F, Weber S, Sad S, de Diego J, Hoops SL, Breiden B, Sandhoff K, Brinkmann V, Kaufmann SH, Schaible UE. Apoptotic vesicles crossprime CD8 T cells and protect against tuberculosis. Immunity 2006;24:105–17

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We wish to thank Brian T. Edelson and Boris Calderon for their assistance in developing the concepts in this manuscript. We also thank Kathy Frederick for her animal husbandry and technical support. This work was supported by grants from the N.I.H.

Author information

Authors and Affiliations

  1. Department of Pathology and Immunology, Washington University School of Medicine, 660 South Euclid Ave., Box 8118, St. Louis, MO, 63110, USA

    Javier A. Carrero & Emil R. Unanue

Authors
  1. Javier A. Carrero
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Emil R. Unanue
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Emil R. Unanue.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Carrero, J.A., Unanue, E.R. Impact of lymphocyte apoptosis on the innate immune stages of infection. Immunol Res 38, 333–341 (2007). https://doi.org/10.1007/s12026-007-0017-z

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12026-007-0017-z

Keywords

Search

Navigation