In addition, uptake of apoptotic debris by competent phagocytes allows efficient cross-presentation of M. tuberculosis antigens [33]. Thus, the avoidance of apoptosis may be considered a virulence mechanism and a recent study has in fact reported a inverse relationship between the intracellular growth
rate and the ability of strains to induce apoptosis [34]. Two previous studies have implicated the 19 kDa as pro-apoptotic [14, 17] and our results, although variable between donors tend to support this conclusion. However the dependence or otherwise on post-translation modification requires additional work as the findings of Lopez et al. suggested that this effect was acylation independent, whereas the trend in our study suggest acylation is necessary (Figure 6). Conclusion In conclusion we have presented further evidence TGF-beta inhibitor of the role of the 19 kDa as a key modulator of the human innate immune
response. There is considerable evidence that the protein downregulates IFN-γ induced macrophage activation, an effect that will tend to favour bacillary survival during the development of an acquired immune response. On the other hand the molecule will tend to give away the presence of bacilli to the innate system early in infection, perhaps teleologically explaining why it is not upregulated early after find more infection [22]. In addition, this work provides further evidence of the utility of defined mutants to delineate Tacrolimus (FK506) key determinants of the innate immune response in the context of whole bacilli. Acknowledgements This work was supported by the Wellcome Trust (Refs. 064261, 060079 and 038997). References 1. Gordon S: Pattern recognition receptors: doubling up for the innate immune response. Cell 2002,111(7):927–930.CrossRefPubMed 2. Takeda
K, Kaisho T, Akira S: Toll-like receptors. Annu Rev Immunol 2003, 21:335–376.CrossRefPubMed 3. Hawn TR, Verbon A, Lettinga KD, Zhao LP, Li SS, Laws RJ, Skerrett SJ, Beutler B, Schroeder L, Nachman A, et al.: A common dominant TLR5 stop codon polymorphism abolishes flagellin signaling and is associated with susceptibility to legionnaires’ disease. J Exp Med 2003,198(10):1563–1572.CrossRefPubMed 4. Poltorak A, He X, Smirnova I, Liu MY, Van Huffel C, Du X, Birdwell D, Alejos E, Silva M, Galanos C, et al.: Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. Science 1998,282(5396):2085–2088.CrossRefPubMed 5. Ozinsky A, Underhill DM, Fontenot JD, Hajjar AM, Smith KD, Wilson CB, Schroeder L, Aderem A: The repertoire for pattern recognition of pathogens by the innate immune system is defined by cooperation between toll-like receptors. Proc Natl Acad Sci USA 2000,97(25):13766–13771.CrossRefPubMed 6. Seya T, Matsumoto M: A lipoprotein family from Mycoplasma fermentans confers host immune activation through Toll-like receptor 2. Int J Biochem Cell Biol 2002,34(8):901–906.