Role of lipids in killing mycobacteria by macrophages: evidence for NF-kappaB-dependent and -independent killing induced by different lipids

Cell Microbiol. 2009 Mar;11(3):406-20. doi: 10.1111/j.1462-5822.2008.01263.x. Epub 2008 Nov 7.


We have shown that several lipids can modulate the macrophage innate immune response against mycobacteria and enhance their killing. Since NF-kappaB is required for mycobacterial killing, we tested the ability of lipids to activate NF-kappaB in uninfected macrophages and those infected with mycobacteria. In uninfected cells, sphingomyelin (SM), phosphatidylinositol-4-phosphate (PIP) and arachidonic acid (AA) enhanced NF-kappaB activation and the cell surface expression of CD69, a macrophage activation marker regulated by NF-kappaB. Sphingosine (Sph), sphingosine-1-phosphate (S1P), diacylglycerol (DAG), eicosapentanoic acid (EPA) and phosphatidyl choline (PC) failed to activate either NF-kappaB or CD69. Ceramide (Cer) activated CD69 expression without activating NF-kappaB. In Mycobacterium smegmatis-infected cells, NF-kappaB was transiently activated in a manner that was enhanced by SM, PIP and AA. In contrast Mycobacterium avium mostly repressed NF-kappaB activation and only SM and AA could induce its partial activation. While lipids that activate NF-kappaB in uninfected cells tend to kill mycobacteria in macrophages Sph and S1P failed to activate NF-kappaB under most conditions but nevertheless enhanced killing of M. smegmatis, M. avium and M. tuberculosis H37Rv. Our results argue that both NF-kappaB-dependent and -independent mechanisms are involved in macrophage killing of mycobacteria and that both mechanisms can be enhanced by selected lipids.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / biosynthesis
  • Antigens, Differentiation, T-Lymphocyte / biosynthesis
  • Cell Line
  • Immunologic Factors / pharmacology*
  • Lectins, C-Type
  • Lipids / pharmacology*
  • Macrophages / immunology*
  • Macrophages / microbiology
  • Mice
  • Mycobacterium avium / immunology*
  • Mycobacterium smegmatis / immunology*
  • Mycobacterium tuberculosis / immunology*
  • NF-kappa B / immunology*


  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • CD69 antigen
  • Immunologic Factors
  • Lectins, C-Type
  • Lipids
  • NF-kappa B