The Journal of Immunology, 2007, 178: 2610-2611.
Copyright © 2007 by The American Association of Immunologists, Inc.
Response to Comment on "Not Lipoteichoic Acid but Lipoproteins Appear to Be the Dominant Immunobiologically Active Compounds in Staphylococcus aureus"
Masahito Hashimoto,
Maiko Furuyashiki and
Yasuo Suda
Department of Nanostructure and Advanced Materials, Kagoshima University, Kagoshima, Japan
Von Aulock et al. demonstrated in their letter (1) that the lipoteichoic acids (LTAs) of Staphylococcus aureus 
lgt mutant and its wild type (WT) are equipotent in stimulating cytokine release in human whole blood. However, we were not able to confirm their results in our experimental systems using human peripheral whole blood or human TLR2-transfected 293T cells (Fig. 1) but proved our previous ones that LTA fraction from mutant was 100-fold less active than WT one using mice system (2).
Stoll et al. (3) reported that cells of S. aureus WT induced stronger inflammatory response than the lgt mutant, whereas the activity of culture supernatants of the mutant were equal or even superior to WT ones. They also observed a synergistic effect of the mutant supernatants with synthetic lipopeptides, suggesting that the mutants released other active molecules. The molecules are expected to be peptidoglycan fragments, which may synergistically activate cells with lipopeptides as Takada et al. (4) pointed out. It was also reported that peptidoglycan fragments do not exhibit apparent activity in mice (4). Thus, the discrepancy may be explained by the amount of contaminants in the LTA fraction due to the difference in the culture condition and/or the separation procedures.
As Von Aulock et al. suggested, we have not measured the levels of the immunobiological activities of the synthetic LTA counterparts they used, nor characterized the structure of active lipoprotein(s). These experiments should be required for the further discussion of activity of LTA molecules themselves. Although LTA molecules might not be completely inactive, it is difficult to consider that LTA molecules are major immunostimulatory principles of Gram-positive bacteria from our results using the knockout strain.
References
- Von Aulock, S., T. hartung, C. Hermann. 2007. Comments on "Not lipoteichoic acid but lipoproteins appear to be the dominant immunobiologically active compounds in Staphylococcus aureus". J. Immunol. 178: 2610[Free Full Text]
- Hashimoto, M., K. Tawaratsumida, H. Kariya, A. Kiyohara, Y. Suda, F. Kirikae, T. Kirikae, F. Gotz. 2006. Not lipoteichoic acid but lipoproteins appear to be the dominant immunobiologically active compounds in Staphylococcus aureus. J. Immunol. 177: 3162-3169. [Abstract/Free Full Text]
- Stoll, H., J. Dengjel, C. Nerz, F. Gotz. 2006. Staphylococcus aureus deficient in lipidation of prelipoproteins is attenuated in growth and immune activation. Infect. Immun. 73: 2411-2423.
- Takada, H., A. Uehara. 2006. Enhancement of TLR-mediated innate immune responses by peptidoglycans through NOD signaling. Curr. Pharm. Des. 12: 4163-4172. [Medline]
induction in human peripheral whole blood. Human peripheral whole blood diluted 1/5 in RPMI 1640 was stimulated for 24 h. TNF-
B activation in human TLR2-transfected 293T cells. 293T cells were transfected with human TLR2 (provided by K. Shibata, Graduate School of Medicine, Hokkaido University, Hokkaido, Japan), pNF