Journal article

Publication year: 2010

Pages: 922-930

Journal: The Journal of Immunology

Volume number: 184

Issue number: 2

ISSN: 0022-1767

eISSN: 1550-6606

DOI Link: https://doi.org/10.4049/jimmunol.0901346

Publisher: American Association of Immunologists

Abstract: 
Different NOD-like receptors, including NLRP1, NLRP3, and NLRC4, as well as the recently identified HIN-200 protein, AIM2, form multiprotein complexes called inflammasomes, which mediate caspase-I-dependent processing of pro-IL-1 beta. Listeria monocytogenes is an intracellular pathogen that is actively phagocytosed by monocytes/macrophages and subsequently escapes from the phagosome into the host cell cytosol, depending on its pore-forming toxin listeriolysin O (LLO). In this study, we demonstrate that human PBMCs produced mature IL-1 beta when infected with wild-type L monocytogenes or when treated with purified LLO. L. monocytogenes mutants lacking LLO or expressing a noncytolytic LLO as well as the avirulent Listeria innocua induced strongly impaired IL-1 beta production. RNA interference and inhibitor experiments in human PBMCs as well as experiments in Nlrp3 and Rip2 knockout bone marrow-derived macrophages demonstrated that the Listeria-induced IL-1 beta release was dependent on ASC, caspase-1, and NLRP3, whereas NOD2, Rip2, NLRP1, NLRP6, NLRP12, NLRC4, and AIM2 appeared to be dispensable. We found that L. monocytogenes-induced IL-1 beta production was largely dependent on phagosomal acidification and cathepsin B release, whereas purified LLO activated an IL-1 beta production independently of these mechanisms. Our results indicate that L monocytogenes-infected human PBMCs produced IL-1 beta, largely depending on an LLO-mediated phagosomal rupture and cathepsin B release, which is sensed by Nlrp3. In addition, an LLO-dependent but cathepsin B-independent NLRP3 activation might contribute to some extent to the IL-1 beta production in L. monocytogenes-infected cells. The Journal of Immunology, 2010,184: 922-930.

Harvard Citation style: Meixenberger, K., Pache, F., Eitel, J., Schmeck, B., Hippenstiel, S., Slevogt, H., et al. (2010) Listeria monocytogenes-Infected Human Peripheral Blood Mononuclear Cells Produce IL-1β, Depending on Listeriolysin O and NLRP3, The Journal of Immunology, 184(2), pp. 922-930. https://doi.org/10.4049/jimmunol.0901346

APA Citation style: Meixenberger, K., Pache, F., Eitel, J., Schmeck, B., Hippenstiel, S., Slevogt, H., N'Guessan, P., Witzenrath, M., Netea, M., Chakraborty, T., Suttorp, N., & Opitz, B. (2010). Listeria monocytogenes-Infected Human Peripheral Blood Mononuclear Cells Produce IL-1β, Depending on Listeriolysin O and NLRP3. The Journal of Immunology. 184(2), 922-930. https://doi.org/10.4049/jimmunol.0901346