Skip to main content
SpringerLink
Log in

Differential regulation of protein kinase C isoforms of macrophages by pathogenic and non-pathogenic mycobacteria

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Given the fact that Mycobacterium tuberculosis (Mtb) may respond to the intracellular milieu of the macrophage with the induction of environmentally regulated genes required for survival and growth of the bacteria we assumed that the protein kinases may also be the factors in Mycobacterium–macrophage interaction. Since, protein kinases play a major role in various critical cellular processes including regulation of immune responses, we describe the fate of expression and phosphorylation of protein kinase C in macrophage cell lines exposed to Mtb H37Rv and raised the question whether the change in the events of expression and phosphorylation are the results of direct interaction of bacilli with macrophages and/or, are also indirectly mediated by specific cytokines that are induced in response to exposure. Our results show that only novel PKCs are phosphorylated during infection of macrophages by pathogenic and non-pathogenic mycobacteria and the alteration is a result of direct host-bacilli association which is independent of cytokines as mediators. Expression of PKC-α (conventional PKC isoform) was down regulated by Mtb H37Rv. In contrast the non-pathogenic fast grower Mycobacterium smegmatis (MS) increased the expression and phosphorylation of PKC-α. PKC-α was also increased in macrophages treated with serum of mice immunized with Mtb H37Rv. The study has shown that pathogenic and non-pathogenic mycobacteria categorically select the type of protein kinases C for activation/deactivation.

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
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Koul A, Herget T, Klebl B, Ullrich A (2004) Interplay between mycobacteria and host signaling pathways. Nat Rev Microbiol 2:189–202. doi:10.1038/nrmicro840

    Article  PubMed  CAS  Google Scholar 

  2. Roach SK, Schorey JS (2002) Differential regulation of the mitogen-activated protein kinases by pathogenic and nonpathogenic mycobacteria. Infect Immun 70:3040–3052. doi:10.1128/IAI.70.6.3040-3052.2002

    Article  PubMed  CAS  Google Scholar 

  3. Schorey JS, Cooper AM (2003) Macrophage signaling upon mycobacterial infection: the MAP kinases lead the way. Cell Microbiol 5:133–142. doi:10.1046/j.1462-5822.2003.00263.x

    Article  PubMed  CAS  Google Scholar 

  4. Platanias LC (2005) Mechanisms of type-I- and type-II-interferon-mediated signaling. Nat Rev Immunol 5:375–386. doi:10.1038/nri1604

    Article  PubMed  CAS  Google Scholar 

  5. Li Y, Srivastava KK, Platanias LC (2004) Mechanisms of type I interferon signaling in normal and malignant cells. Arch Immunol Ther Exp (Warsz) 52:156–163

    CAS  Google Scholar 

  6. Srivastava KK, Batra S, Sassano A, Li Y, Majchrzak B, Kiyokawa H et al (2004) Engagement of protein kinase C-θ in interferon signaling in T-cells. J Biol Chem 279:29911–29920. doi:10.1074/jbc.M401997200

    Article  PubMed  CAS  Google Scholar 

  7. Webb BLJ, Hirst SJ, Giembycz MA (2000) Protein kinase C isoenzymes: a review of their structure, regulation and role in regulating airways smooth muscle tone and mitogenesis. Br J Pharmacol 130:1433–1452. doi:10.1038/sj.bjp. 0703452

    Article  PubMed  CAS  Google Scholar 

  8. Chen C, Chen YH, Lin WW (1999) Involvement of p38 mitogen-activated protein kinase in lipopolysaccharide-induced iNOS and COX-2 expression in J774 macrophages. Immunology 97:24–129. doi:10.1046/j.1365-2567.1999.00747.x

    Article  Google Scholar 

  9. Olivier M, Cook P, Desanctis J, Hel Z, Wojciechowski W, Reiner NE et al (1998) Phenotypic difference between Bcg(r) and Bcg(s) macrophages is related to differences in protein-kinase-C-dependent signaling. Eur J Biochem 251:734–743. doi:10.1046/j.1432-1327.1998.2510734.x

    Article  PubMed  CAS  Google Scholar 

  10. Kusner DJ, Barton JA (2001) ATP stimulates human macrophages to kill intracellular virulent Mycobacterium tuberculosis via calcium-dependent phagosome-lysosome fusion. J Immunol 167:3308–3315

    PubMed  CAS  Google Scholar 

  11. Malik ZA, Denning GM, Kusner DJ (2000) Inhibition of Ca2+ signaling by Mycobacterium tuberculosis is associated with reduced phagosome-lysosome fusion and increased survival within human macrophages. J Exp Med 191:287–302. doi:10.1084/jem.191.2.287

    Article  PubMed  CAS  Google Scholar 

  12. Malik ZA, Iyer SS, Kusner DJ (2001) Mycobacterium tuberculosis phagosomes exhibit altered calmodulin-dependent signal transduction: contribution to inhibition of phagosome-lysosome fusion and intracellular survival in human macrophages. J Immunol 166:3392–3401

    PubMed  CAS  Google Scholar 

  13. Fratti RA, Chaua J, Vergne I, Deretic V (2003) Mycobacterium tuberculosis glycosylated phosphatidylinositol causes phagosome maturation arrest. Proc Natl Acad Sci USA 100:5437–5442. doi:10.1073/pnas.0737613100

    Article  PubMed  CAS  Google Scholar 

  14. Fratazzi C, Arbeit RD, Carini C, Remold HG (1997) Programmed cell death of Mycobacterium avium serovar 4- infected human macrophages prevents the mycobacteria from spreading and induces mycobacterial growth inhibition by freshly added, uninfected macrophages. J Immunol 158:4320–4327

    PubMed  CAS  Google Scholar 

  15. Bhattacharyya A, Pathak S, Kundu M, Basu J (2002) Mitogen activated protein kinases regulate Mycobacterium avium-induced tumor necrosis factor-a release from macrophages. FEMS Immunol Med Microbiol 34:73–80

    PubMed  CAS  Google Scholar 

  16. Bhattacharyya S, Ghosh S, Sen P, Roy S, Majumdar S (2001) Selective impairment of protein kinase C isotypes in murine macrophage by Leishmania donovani. Mol Cell Biochem 216:47–57. doi:10.1023/A:1011048210691

    Article  PubMed  CAS  Google Scholar 

  17. Anik SD, Vassiliki C, Francine G, Descoteaux A (1999) Role of protein kinase C-α in the control of infection by intracellular pathogens in macrophages. J Immunol 163:5505–5511

    Google Scholar 

  18. Holm A, Tejle K, Gunnarsson T, Magnusson KE, Descoteaux A, Rasmusson B (2003) Role of protein kinase C-α for uptake of unopsonized prey and phagosomal maturation in macrophages. Biochem Biophys Res Commun 302:653–658. doi:10.1016/S0006-291X(03)00231-6

    Article  PubMed  CAS  Google Scholar 

  19. Segura M, Gottschalk M, Olivier M (2004) Encapsulated Streptococcus suis inhibits activation of signaling pathways involved in phagocytosis. Infect Immun 72:5322–5330. doi:10.1128/IAI.72.9.5322-5330.2004

    Article  PubMed  CAS  Google Scholar 

  20. Yan Hing DJN, Desjardins M, Descoteauxa A (2004) Proteomic analysis reveals a role for protein kinase C-α in phagosome maturation. Biochem Biophys Res Commun 319:810–816. doi:10.1016/j.bbrc.2004.05.054

    Article  Google Scholar 

  21. Breton A, Descoteaux A (2000) Protein kinase C-α participates in FcγR-mediated phagocytosis in macrophages. Biochem Biophys Res Commun 276:472–476. doi:10.1006/bbrc.2000.3511

    Article  PubMed  CAS  Google Scholar 

  22. Stamm LM, Morisaki JH, Gao LY, Jeng RL, McDonald KL, Roth R et al (2003) Mycobacterium marinum escapes from phagosomes and is propelled by actin-based motility. J Exp Med 198:1361–1368. doi:10.1084/jem.20031072

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgment

We thank Director, CDRI for his encouragement and support. Technical assistance by Mr. A. P. Singh is appreciated. SKC is recipient of CSIR-UGC Fellowship. The communication number assigned to this manuscript by CDRI is 7118.

Author information

Authors and Affiliations

  1. Division of Microbiology, Central Drug Research Institute, Lucknow, 226001, India

    Shivendra K. Chaurasiya & Kishore K. Srivastava

Authors
  1. Shivendra K. Chaurasiya
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kishore K. Srivastava
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kishore K. Srivastava.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chaurasiya, S.K., Srivastava, K.K. Differential regulation of protein kinase C isoforms of macrophages by pathogenic and non-pathogenic mycobacteria. Mol Cell Biochem 318, 167–174 (2008). https://doi.org/10.1007/s11010-008-9866-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-008-9866-6

Keywords

Search

Navigation