Skip to main content
Journal cover image

Mycobacteria manipulate macrophage recruitment through coordinated use of membrane lipids.

Publication ,  Journal Article
Cambier, CJ; Takaki, KK; Larson, RP; Hernandez, RE; Tobin, DM; Urdahl, KB; Cosma, CL; Ramakrishnan, L
Published in: Nature
January 9, 2014

The evolutionary survival of Mycobacterium tuberculosis, the cause of human tuberculosis, depends on its ability to invade the host, replicate, and transmit infection. At its initial peripheral infection site in the distal lung airways, M. tuberculosis infects macrophages, which transport it to deeper tissues. How mycobacteria survive in these broadly microbicidal cells is an important question. Here we show in mice and zebrafish that M. tuberculosis, and its close pathogenic relative Mycobacterium marinum, preferentially recruit and infect permissive macrophages while evading microbicidal ones. This immune evasion is accomplished by using cell-surface-associated phthiocerol dimycoceroserate (PDIM) lipids to mask underlying pathogen-associated molecular patterns (PAMPs). In the absence of PDIM, these PAMPs signal a Toll-like receptor (TLR)-dependent recruitment of macrophages that produce microbicidal reactive nitrogen species. Concordantly, the related phenolic glycolipids (PGLs) promote the recruitment of permissive macrophages through a host chemokine receptor 2 (CCR2)-mediated pathway. Thus, we have identified coordinated roles for PDIM, known to be essential for mycobacterial virulence, and PGL, which (along with CCR2) is known to be associated with human tuberculosis. Our findings also suggest an explanation for the longstanding observation that M. tuberculosis initiates infection in the relatively sterile environment of the lower respiratory tract, rather than in the upper respiratory tract, where resident microflora and inhaled environmental microbes may continually recruit microbicidal macrophages through TLR-dependent signalling.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Nature

DOI

EISSN

1476-4687

Publication Date

January 9, 2014

Volume

505

Issue

7482

Start / End Page

218 / 222

Location

England

Related Subject Headings

  • Zebrafish
  • Virulence
  • Toll-Like Receptors
  • Receptors, CCR2
  • Mycobacterium tuberculosis
  • Mycobacterium
  • Mice, Inbred C57BL
  • Mice
  • Membrane Lipids
  • Macrophages
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Cambier, C. J., Takaki, K. K., Larson, R. P., Hernandez, R. E., Tobin, D. M., Urdahl, K. B., … Ramakrishnan, L. (2014). Mycobacteria manipulate macrophage recruitment through coordinated use of membrane lipids. Nature, 505(7482), 218–222. https://doi.org/10.1038/nature12799
Cambier, C. J., Kevin K. Takaki, Ryan P. Larson, Rafael E. Hernandez, David M. Tobin, Kevin B. Urdahl, Christine L. Cosma, and Lalita Ramakrishnan. “Mycobacteria manipulate macrophage recruitment through coordinated use of membrane lipids.Nature 505, no. 7482 (January 9, 2014): 218–22. https://doi.org/10.1038/nature12799.
Cambier CJ, Takaki KK, Larson RP, Hernandez RE, Tobin DM, Urdahl KB, et al. Mycobacteria manipulate macrophage recruitment through coordinated use of membrane lipids. Nature. 2014 Jan 9;505(7482):218–22.
Cambier, C. J., et al. “Mycobacteria manipulate macrophage recruitment through coordinated use of membrane lipids.Nature, vol. 505, no. 7482, Jan. 2014, pp. 218–22. Pubmed, doi:10.1038/nature12799.
Cambier CJ, Takaki KK, Larson RP, Hernandez RE, Tobin DM, Urdahl KB, Cosma CL, Ramakrishnan L. Mycobacteria manipulate macrophage recruitment through coordinated use of membrane lipids. Nature. 2014 Jan 9;505(7482):218–222.
Journal cover image

Published In

Nature

DOI

EISSN

1476-4687

Publication Date

January 9, 2014

Volume

505

Issue

7482

Start / End Page

218 / 222

Location

England

Related Subject Headings

  • Zebrafish
  • Virulence
  • Toll-Like Receptors
  • Receptors, CCR2
  • Mycobacterium tuberculosis
  • Mycobacterium
  • Mice, Inbred C57BL
  • Mice
  • Membrane Lipids
  • Macrophages