ADP-heptose: a bacterial PAMP detected by the host sensor ALPK1 - Sorbonne Université
Journal Articles Cellular and Molecular Life Sciences Year : 2021

ADP-heptose: a bacterial PAMP detected by the host sensor ALPK1

Abstract

The innate immune response constitutes the first line of defense against pathogens. It involves the recognition of pathogen-associated molecular patterns (PAMPs) by pathogen recognition receptors (PRRs), the production of inflammatory cytokines and the recruitment of immune cells to infection sites. Recently, ADP-heptose, a soluble intermediate of the lipopolysaccharide biosynthetic pathway in Gram-negative bacteria, has been identified by several research groups as a PAMP. Here, we recapitulate the evidence that led to this identification and discuss the controversy over the immunogenic properties of heptose 1,7-bisphosphate (HBP), another bacterial heptose previously defined as an activator of innate immunity. Then, we describe the mechanism of ADP-heptose sensing by alpha-protein kinase 1 (ALPK1) and its downstream signaling pathway that involves the proteins TIFA and TRAF6 and induces the activation of NF-κB and the secretion of inflammatory cytokines. Finally, we discuss possible delivery mechanisms of ADP-heptose in cells during infection, and propose new lines of thinking to further explore the roles of the ADP-heptose/ALPK1/TIFA axis in infections and its potential implication in the control of intestinal homeostasis.
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Dates and versions

hal-03987835 , version 1 (14-02-2023)

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Diego García-Weber, Cécile Arrieumerlou. ADP-heptose: a bacterial PAMP detected by the host sensor ALPK1. Cellular and Molecular Life Sciences, 2021, 78 (1), pp.17-29. ⟨10.1007/s00018-020-03577-w⟩. ⟨hal-03987835⟩
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