PMID- 10490993
OWN - NLM
STAT- MEDLINE
DCOM- 19991021
LR  - 20171116
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 163
IP  - 7
DP  - 1999 Oct 1
TI  - Human toll-like receptors mediate cellular activation by Mycobacterium
      tuberculosis.
PG  - 3920-7
AB  - Recent studies have implicated a family of mammalian Toll-like receptors (TLR) in
      the activation of macrophages by Gram-negative and Gram-positive bacterial
      products. We have previously shown that different TLR proteins mediate cellular
      activation by the distinct CD14 ligands Gram-negative bacterial LPS and
      mycobacterial glycolipid lipoarabinomannan (LAM). Here we show that viable
      Mycobacterium tuberculosis bacilli activated both Chinese hamster ovary cells and
      murine macrophages that overexpressed either TLR2 or TLR4. This contrasted with
      Gram-positive bacteria and Mycobacterium avium, which activated cells via TLR2
      but not TLR4. Both virulent and attenuated strains of M. tuberculosis could
      activate the cells in a TLR-dependent manner. Neither membrane-bound nor soluble 
      CD14 was required for bacilli to activate cells in a TLR-dependent manner. We
      also assessed whether LAM was the mycobacterial cell wall component responsible
      for TLR-dependent cellular activation by M. tuberculosis. We found that TLR2, but
      not TLR4, could confer responsiveness to LAM isolated from rapidly growing
      mycobacteria. In contrast, LAM isolated from M. tuberculosis or Mycobacterium
      bovis bacillus Calmette-Guerin failed to induce TLR-dependent activation. Lastly,
      both soluble and cell wall-associated mycobacterial factors were capable of
      mediating activation via distinct TLR proteins. A soluble heat-stable and
      protease-resistant factor was found to mediate TLR2-dependent activation, whereas
      a heat-sensitive cell-associated mycobacterial factor mediated TLR4-dependent
      activation. Together, our data demonstrate that Toll-like receptors can mediate
      cellular activation by M. tuberculosis via CD14-independent ligands that are
      distinct from the mycobacterial cell wall glycolipid LAM.
FAU - Means, T K
AU  - Means TK
AD  - Pulmonary Center, Boston University School of Medicine, Boston Medical Center, MA
      02118, USA.
FAU - Wang, S
AU  - Wang S
FAU - Lien, E
AU  - Lien E
FAU - Yoshimura, A
AU  - Yoshimura A
FAU - Golenbock, D T
AU  - Golenbock DT
FAU - Fenton, M J
AU  - Fenton MJ
LA  - eng
GR  - GM54060/GM/NIGMS NIH HHS/United States
GR  - HL55681/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Acute-Phase Proteins)
RN  - 0 (Bacterial Proteins)
RN  - 0 (Carrier Proteins)
RN  - 0 (Drosophila Proteins)
RN  - 0 (Lipopolysaccharide Receptors)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Mannans)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (TLR2 protein, human)
RN  - 0 (TLR4 protein, human)
RN  - 0 (Toll-Like Receptor 2)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (Toll-Like Receptors)
RN  - 0 (lipoarabinomannan)
RN  - 0 (lipopolysaccharide-binding protein)
RN  - 53026-40-7 (arabinomannan)
SB  - AIM
SB  - IM
MH  - *Acute-Phase Proteins
MH  - Animals
MH  - Bacterial Proteins/physiology
MH  - CHO Cells
MH  - Carrier Proteins/physiology
MH  - Cell Line
MH  - Cricetinae
MH  - *Drosophila Proteins
MH  - Fibroblasts/immunology/*metabolism/*microbiology
MH  - Humans
MH  - Lipopolysaccharide Receptors/physiology
MH  - Lipopolysaccharides/metabolism/pharmacology
MH  - *Macrophage Activation/immunology
MH  - Mannans/pharmacology
MH  - Membrane Glycoproteins/*physiology
MH  - Mice
MH  - Mycobacterium tuberculosis/growth & development/immunology/*physiology
MH  - Receptors, Cell Surface/*physiology
MH  - Solubility
MH  - Toll-Like Receptor 2
MH  - Toll-Like Receptor 4
MH  - Toll-Like Receptors
EDAT- 1999/09/22 00:00
MHDA- 1999/09/22 00:01
CRDT- 1999/09/22 00:00
PHST- 1999/09/22 00:00 [pubmed]
PHST- 1999/09/22 00:01 [medline]
PHST- 1999/09/22 00:00 [entrez]
AID - ji_v163n7p3920 [pii]
PST - ppublish
SO  - J Immunol. 1999 Oct 1;163(7):3920-7.