TLR2 and Its Co-Receptors Determine Responses of Macrophages and Dendritic Cells to Lipoproteins of Mycobacterium Tuberculosis

Cell Immunol. 2009;258(1):29-37. doi: 10.1016/j.cellimm.2009.03.008. Epub 2009 Apr 11.

Abstract

Mycobacterium tuberculosis (Mtb) signals through Toll-like receptor 2 (TLR2) to regulate antigen presenting cells (APCs). Mtb lipoproteins, including LpqH, LprA, LprG and PhoS1, are TLR2 agonists, but their co-receptor requirements are unknown. We studied Mtb lipoprotein-induced responses in TLR2(-/-), TLR1(-/-), TLR6(-/-), CD14(-/-) and CD36(-/-) macrophages. Responses to LprA, LprG, LpqH and PhoS1 were completely dependent on TLR2. LprG, LpqH, and PhoS1 were dependent on TLR1, but LprA did not require TLR1. None of the lipoproteins required TLR6, although a redundant contribution by TLR6 cannot be excluded. CD14 contributed to detection of LprA, LprG and LpqH, whereas CD36 contributed only to detection of LprA. Studies of lung APC subsets revealed lower TLR2 expression by CD11b(high)/CD11c(low) lung macrophages than CD11b(low)/CD11c(high) alveolar macrophages, which correlated with hyporesponsiveness of lung macrophages to LpqH. Thus, lung APC subsets differ in TLR expression, which may determine differences in responses to Mtb.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antigens, Bacterial / immunology
  • Antigens, Bacterial / pharmacology
  • CD36 Antigens / genetics
  • CD36 Antigens / immunology*
  • CD36 Antigens / metabolism
  • Cell Line
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology*
  • Dendritic Cells / microbiology
  • Female
  • Humans
  • Lipopolysaccharide Receptors / genetics
  • Lipopolysaccharide Receptors / immunology
  • Lipopolysaccharide Receptors / metabolism
  • Lipoproteins / immunology*
  • Macrophages / drug effects
  • Macrophages / immunology*
  • Macrophages / microbiology
  • Mice
  • Mice, Inbred C57BL
  • Mycobacterium tuberculosis / immunology*
  • Toll-Like Receptor 1 / genetics
  • Toll-Like Receptor 1 / immunology
  • Toll-Like Receptor 1 / metabolism
  • Toll-Like Receptor 2 / agonists
  • Toll-Like Receptor 2 / genetics
  • Toll-Like Receptor 2 / immunology*
  • Toll-Like Receptor 6 / genetics
  • Toll-Like Receptor 6 / immunology
  • Toll-Like Receptor 6 / metabolism

Substances

  • Antigens, Bacterial
  • CD36 Antigens
  • Lipopolysaccharide Receptors
  • Lipoproteins
  • Toll-Like Receptor 1
  • Toll-Like Receptor 2
  • Toll-Like Receptor 6