Characterization of the Inflammasome in Human Kupffer Cells in Response to Synthetic Agonists and Pathogens.

Abstract

The liver is the largest gland in the human body and functions as an innate immune organ. Liver macrophages called Kupffer cells (KC) constitute the largest group of macrophages in the human body. Innate immune responses involving KC represent the first line of defense against pathogens in the liver. Human monocyte-derived macrophages have been used to characterize inflammasome responses that lead to the release of the proinflammatory cytokines IL-1β and IL-18, but it has not yet been determined whether human KC contain functional inflammasomes. We show, to our knowledge for the first time, that KC express genes and proteins that make up several different inflammasome complexes. Moreover, activation of KC in response to the absent in melanoma 2 (AIM2) inflammasome led to the production of IL-1β and IL-18, which activated IL-8 transcription and hepatic NK cell activity, respectively. Other inflammasome responses were also activated in response to selected bacteria and viruses. However, hepatitis B virus inhibited the AIM2 inflammasome by reducing the mRNA stability of IFN regulatory factor 7, which regulated AIM2 transcription. These data demonstrate the production of IL-1β and IL-18 in KC, suggesting that KC contain functional inflammasomes that could be important players in the innate immune response following certain infections of the liver. We think our findings could potentially aid therapeutic approaches against chronic liver diseases that activate the inflammasome.

DOI: 10.4049/jimmunol.1502301

Cite this paper

@article{Zannetti2016CharacterizationOT, title={Characterization of the Inflammasome in Human Kupffer Cells in Response to Synthetic Agonists and Pathogens.}, author={Claudia Zannetti and Guillaume G Roblot and Emily Charrier and Michelle Ainouze and Issam Tout and François Briat and Nathalie Isorce and Suzanne Faure-Dupuy and Maud Michelet and Marie Marotel and Semra Kati and Thomas F Schulz and Michel Rivoire and Alexandra Traverse-Glehen and Souphalone Luangsay and Omran Alatiff and Thomas Henry and Thierry Walzer and David Durantel and Uzma Ayesha Hasan}, journal={Journal of immunology}, year={2016}, volume={197 1}, pages={356-67} }