Human caspase-4 detects tetra-acylated LPS and cytosolic Francisella and functions differently from murine caspase-11

Brice Lagrange, Sacha Benaoudia, Pierre Wallet, Flora Magnotti, Angelina Provost, Fanny Michal, Amandine Martin, Flaviana Di Lorenzo, Bénédicte F. Py, Antonio Molinaro and Thomas Henry ()
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Brice Lagrange: Univ Lyon
Sacha Benaoudia: Univ Lyon
Pierre Wallet: Univ Lyon
Flora Magnotti: Univ Lyon
Angelina Provost: Univ Lyon
Fanny Michal: Univ Lyon
Amandine Martin: Univ Lyon
Flaviana Di Lorenzo: University of Napoli Federico II, Complesso Universitario Monte Santangelo
Bénédicte F. Py: Univ Lyon
Antonio Molinaro: University of Napoli Federico II, Complesso Universitario Monte Santangelo
Thomas Henry: Univ Lyon

Nature Communications, 2018, vol. 9, issue 1, 1-14

Abstract: Abstract Caspase-4/5 in humans and caspase-11 in mice bind hexa-acylated lipid A, the lipid moeity of lipopolysaccharide (LPS), to induce the activation of non-canonical inflammasome. Pathogens such as Francisella novicida express an under-acylated lipid A and escape caspase-11 recognition in mice. Here, we show that caspase-4 drives inflammasome responses to F. novicida infection in human macrophages. Caspase-4 triggers F. novicida-mediated, gasdermin D-dependent pyroptosis and activates the NLRP3 inflammasome. Inflammasome activation could be recapitulated by transfection of under-acylated LPS from different bacterial species or synthetic tetra-acylated lipid A into cytosol of human macrophage. Our results indicate functional differences between human caspase-4 and murine caspase-11. We further establish that human Guanylate-binding proteins promote inflammasome responses to under-acylated LPS. Altogether, our data demonstrate a broader reactivity of caspase-4 to under-acylated LPS than caspase-11, which may have important clinical implications for management of sepsis.

Date: 2018
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-017-02682-y

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DOI: 10.1038/s41467-017-02682-y

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