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.

  • Correspondence
  • Published:

The Lrp of Mycobacterium tuberculosis regulates the innate immune response of macrophages

Cellular & Molecular Immunology volume 15, pages 934–936 (2018)Cite this article

Mycobacterium tuberculosis (Mtb) is the pathogenic bacteria that causes one-third of tuberculosis infections globally, but the mechanism of its pathogenesis has not been fully elucidated.1 The main pathway by which Mtb infects humans is via the pneogaster; thus, the lung is the main reservoir where Mtb exists. However, Mtb can also infect other human organs. Mtb is an intracellular bacterium of immune cells and, interestingly, it can escape elimination by the host immune system.2 To date, the Bacillus Calmette–Guerin vaccine is the only vaccine that has proved effective and has been approved worldwide. This vaccine was developed by two French scientists, namely, Leon Calmette and Guerin.3

After infecting the human body, Mtb can cause an immune response, including the innate immune response and adaptive immune response.4 Many pathogenic bacteria have conserved molecular patterns called pathogen-associated molecular patterns (PAMPs), many of which induce signaling through Toll-like receptors (TLRs) expressed on innate immune cells.5 The TLR family belongs to pattern-recognition receptors that recognize the PAMPs of bacteria; such PAMPs include lipopolysaccharide (LPS), peptidoglycan, zymosan and bacterial DNA.6 Certain studies have shown that during the early stage of Mtb infection, TLRs have an important function and affect the subsequent activation of immune cells.7 Although research has elucidated the means by which Mtb infects humans and the way in which the body's immune response protects against the mycobacterium, how Mtb evades immune clearance by the host and survives in macrophages remains unknown.8 Hence, this aspect of Mtb pathology has gained increasing attention. Mtb can survive in both monocytes and macrophages.9 There are no symptoms of Mtb bacillus during the incubation period, at which time it is very difficult to treat tuberculosis.10 The protein family including the leucine-responsive regulatory protein (Lrp/AsnC) has been found to play an important role in the nutritional regulation of Mtb, so Lrp must be studied further with respect to its role in Mtb.11 Lrp serves as the paranuclein of Mtb and, hence, has been highly conserved. Lrp (Rv2779c) exists in Mtb H37Rv, but little has been reported concerning the influence of Lrp on the host immune system.

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

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

Figure 1

References

  1. Gandhi NR, Nunn P, Dheda K, Schaaf HS, Zignol M, Soolingen DV et al. Multidrug-resistant and extensively drug-resistant tuberculosis: a threat to global control of tuberculosis. Lancet 2010; 375: 1830–1843.

    Article  Google Scholar 

  2. Pathak SK, Basu S, Basu KK, Banerjee A, Pathak S, Bhattacharyya A et al. Direct extracellular interaction between the early secreted antigen ESAT-6 of Mycobacterium tuberculosis and TLR2 inhibits TLR signaling in macrophages. Nat Immunol 2007; 8: 610–618.

    Article  CAS  Google Scholar 

  3. Andersen P, Doherty TM. The success and failure of BCG - implications for a novel tuberculosis vaccine. Nat Rev Microbiol 2005; 3: 656–662.

    Article  CAS  Google Scholar 

  4. Chen ST, Li JY, Zhang Y, Gao X, Cai H. Recombinant MPT83 derived from Mycobacterium tuberculosis induces cytokine production and upregulates the function of mouse macrophages through TLR2. J Immunol 2012; 188: 668–677.

    Article  CAS  Google Scholar 

  5. Li JY, Liu Y, Gao XX, Gao X, Cai H et al. TLR2 and TLR4 signaling pathways are required for recombinant Brucella abortus BCSP31-induced cytokine production, functional upregulation of mouse macrophages, and the Th1 immune response in vivo and in vitro. Cell Mol Immunol 2014; 11 (5): 477–494.

    Article  CAS  Google Scholar 

  6. Brightbill HD, Libraty DH, Krutzik SR, Yang RB, Belisle JT, Bleharski JR et al. Host defense mechanisms triggered by microbial lipoproteins through toll-like receptors. Science 1999; 285: 732–736.

    Article  CAS  Google Scholar 

  7. Underhill DM, Ozinsky A, Smith KD, Aderem A. Toll-like receptor-2 mediates mycobacteria-induced proinflammatory signaling in macrophages. Proc Natl Acad Sci USA 1999; 96: 14459–14463.

    Article  CAS  Google Scholar 

  8. O'Garra A, Redford PS, McNab FW, Bloom CI, Wilkinson RJ, Berry MP. The immune response in tuberculosis. Annu Rev Immunol 2013; 31: 475–527.

    Article  CAS  Google Scholar 

  9. Malik ZA, Denning GM, Kusner DJ. Inhibition of Ca(2+ signaling by Mycobacterium tuberculosis is associated with reduced phagosome-lysosome fusion and increased survival within human macrophages. J Exp Med 2000; 191: 287–302.

    Article  CAS  Google Scholar 

  10. Wayne LG, Sohaskey CD. Nonreplicating persistence of Mycobacterium tuberculosis. Annu Rev Microbiol 2001; 55: 139–163.

    Article  CAS  Google Scholar 

  11. Deng W, Wang H, Xie J. Regulatory and pathogenesis roles of Mycobacterium Lrp/AsnC family transcriptional factors. J Cell Biochem 2011; 112: 2655–2662.

    Article  CAS  Google Scholar 

  12. Liu Y, Li JY, Chen ST, Huang HR, Cai H. The rLrp of Mycobacterium tuberculosis inhibits proinflammatory cytokine production and downregulates apc function in mouse macrophages via a TLR2-mediated PI3K/Akt pathway activation-dependent mechanism. Cell Mol Immunol 2016; 13 (6): 729–746.

    Article  CAS  Google Scholar 

  13. Gutierrez MG, Master SS, Singh SB, Taylor GA, Colombo MI, Deretic V. Autophagy is a defense mechanism inhibiting BCG and Mycobacterium tuberculosis survival in infected macrophages. Cell 2004; 119: 753–766.

    Article  CAS  Google Scholar 

  14. Singh CR, Moulton RA, Armitige LY, Bidani A, Snuggs M, Dhandayuthapani S et al. Processing and presentation of a mycobacterial antigen 85B epitope by murine macrophages is dependent on the phagosomal acquisition of vacuolar proton ATPase and in situ activation of cathepsin D. J Immunol 2006; 177: 3250–3259.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. State Key Laboratory of Protein and Plant Gene Research, College of Life Sciences, Peking University, 100871, Beijing, China

    Yuan Liu & Hong Cai

Authors
  1. Yuan Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hong Cai
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hong Cai.

Ethics declarations

Conflict of interest

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Liu, Y., Cai, H. The Lrp of Mycobacterium tuberculosis regulates the innate immune response of macrophages. Cell Mol Immunol 15, 934–936 (2018). https://doi.org/10.1038/cmi.2018.6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/cmi.2018.6

Keywords

Search

Advanced search

Quick links