NAD+ prevents septic shock-induced death by non-canonical inflammasome blockade and IL-10 cytokine production in macrophages-Reference-Cited by-同舟云学术

NAD+ prevents septic shock-induced death by non-canonical inflammasome blockade and IL-10 cytokine production in macrophages

Published:2024-01-04 Issue: Volume: Page:
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Author:

Iske Jasper¹²^ORCID,El Fatimy Rachid³⁴^ORCID,Nian Yeqi²⁵,Ghouzlani Amina⁶,Eskandari Siawosh K.⁷,Cetina Biefer Hector Rodriguez¹⁸^ORCID,Vasudevan Anju⁹^ORCID,Elkhal Abdallah⁶^ORCID

Affiliation:

1. Division of Transplant Surgery, Department of Surgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA

2. Department of Cardiothoracic and Vascular Surgery, Germany Heart Center Berlin, Berlin, Germany

3. Department of Neurology, Ann Romney Center for Neurologic Diseases, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA

4. Institute of Biological Sciences (ISSB-P), Mohammed VI Polytechnic University (UM6P), 43150, Benguerir, Morocco

5. Institute of Transplant Medicine, Tianjin First Central Hospital, Nankai University, Tianjin 300192, China

6. NAD+ Immunology Laboratory, Huntington Medical Research Institutes, Pasadena, CA, USA

7. Department of Internal Medicine, University of Groningen, Groningen, Netherlands

8. Department of Cardiac Surgery, Stadtspital Zurich Triemli, Zurich, Switzerland

9. Angiogenesis and Brain Development Laboratory, Huntington Medical Research Institutes, Pasadena, CA, USA

Abstract

Septic shock is characterized by an excessive inflammatory response depicted in a cytokine storm that results from invasive bacterial, fungi, protozoa, and viral infections. Non-canonical inflammasome activation is crucial in the development of septic shock promoting pyroptosis and pro-inflammatory cytokine production via caspase-11 and Gasdermin-D (GSDMD). Here, we show that NAD+ treatment protected mice towards bacterial and LPS induced endotoxic shock by blocking the non-canonical inflammasome specifically. NAD+ administration impeded systemic IL-1β and IL-18 production and GSDMD-mediated pyroptosis of macrophages via the IFN-β/STAT-1 signaling machinery. More importantly, NAD+ administration not only improved casp-11-/- survival but rendered WT mice completely resistant to septic shock via the IL-10 signaling pathway that was independent from the non-canonical inflammasome. Here, we delineated a two-sided effect of NAD+ blocking septic shock through a specific inhibition of the non-canonical inflammasome and promoting immune homeostasis via IL-10, underscoring its unique therapeutic potential.

Publisher

eLife Sciences Publications, Ltd

Link

https://elifesciences.org/reviewed-preprints/88686v2/pdf