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

Claudia Zannetti; Guillaume Roblot; Emily Charrier; Michelle Ainouze; Issam Tout; François Briat; Nathalie Isorce; Suzanne Faure-Dupuy; Maud Michelet; Marie Marotel; Semra Kati; Thomas F. Schulz; Michel Rivoire; Alexandra Traverse-Glehen; Souphalone Luangsay; Omran Alatiff; Thomas Henry; Thierry Walzer; David Durantel; Uzma Hasan

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

Claudia Zannetti ¹ Guillaume Roblot ¹ Emily Charrier ¹ Michelle Ainouze ¹ Issam Tout ¹ François Briat ¹ Nathalie Isorce ¹ Suzanne Faure-Dupuy ² Maud Michelet ² Marie Marotel ¹ Semra Kati Thomas F. Schulz ³ Michel Rivoire ^{4, 5} Alexandra Traverse-Glehen ^{6, 2} Souphalone Luangsay ² Omran Alatiff ⁷ Thomas Henry ⁸ Thierry Walzer ¹ David Durantel ² Uzma Hasan ²

1 Réponse immunitaire innée dans les maladies infectieuses et auto-immunes – Innate immunity in infectious and autoimmune diseases

CIRI - Centre International de Recherche en Infectiologie - UMR

2 CRCL - Centre de Recherche en Cancérologie de Lyon

3 Department of Virology

4 Service d'Oncologie Chirurgicale [Lyon]

5 LabTAU - Application des ultrasons à la thérapie

6 Laboratoire d'anatomie et de cytopathologie - Centre hospitalier Lyon Sud

7 2-BIBS - BioInformatique et BioStatistiques

CIRI - Centre International de Recherche en Infectiologie - UMR

8 Inflammasome, Infections bactériennes et autoinflammation ; Inflammasome, Bacterial Infections and Autoinflammation

CIRI - Centre International de Recherche en Infectiologie - UMR

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-1beta 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-1beta 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-1beta 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

Keywords : agonists Cells Liver Macrophages Proteins Time Melanoma Viruses virology Infection France Inflammasomes Germany Hepatitis Hepatitis B Hepatitis B virus Cytokines

Document type :

Journal articles

Domain :

Life Sciences [q-bio] / Cancer

Complete list of metadatas

https://hal-univ-lyon1.archives-ouvertes.fr/hal-01796202
Contributor : Lauriane Pillet <>
Submitted on : Saturday, May 19, 2018 - 11:34:42 AM
Last modification on : Tuesday, September 24, 2019 - 4:16:08 PM

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

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

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