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Hayley I. Muendlein
Tufts University
3Publications
3H-index
69Citations
Publications 4
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#1Hayley I. Muendlein (Tufts University)H-Index: 3
#2Joseph Sarhan (Tufts University)H-Index: 3
Last.Soroush Tahmasebi (McGill University)H-Index: 8
view all 13 authors...
Summary Receptor-interacting protein kinase 1 (RIPK1) and 3 (RIPK3) are well known for their capacity to drive necroptosis via mixed-lineage kinase-like domain (MLKL). Recently, RIPK1/3 kinase activity has been shown to drive inflammation via activation of MAPK signaling. However, the regulatory mechanisms underlying this kinase-dependent cytokine production remain poorly understood. In the present study, we establish that the kinase activity of RIPK1/3 regulates cytokine translation in mouse an...
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#1Joseph Sarhan (Tufts University)H-Index: 3
#2Beiyun C. Liu (Tufts University)H-Index: 6
Last.Alexander PoltorakH-Index: 18
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Interferons (IFNs) are critical determinants in immune-competence and autoimmunity, and are endogenously regulated by a low-level constitutive feedback loop. However, little is known about the functions and origins of constitutive IFN. Recently, lipopolysaccharide (LPS)-induced IFN was implicated as a driver of necroptosis, a necrotic form of cell death downstream of receptor-interacting protein (RIP) kinase activation and executed by mixed lineage kinase like-domain (MLKL) protein. We found tha...
15 CitationsSource
#1Joseph Sarhan (Tufts University)H-Index: 3
#2Beiyun C. Liu (Tufts University)H-Index: 6
Last.Alexander Poltorak (Tufts University)H-Index: 18
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Cell death and inflammation are intimately linked during Yersinia infection. Pathogenic Yersinia inhibits the MAP kinase TGFβ-activated kinase 1 (TAK1) via the effector YopJ, thereby silencing cytokine expression while activating caspase-8–mediated cell death. Here, using Yersinia pseudotuberculosis in corroboration with costimulation of lipopolysaccharide and (5Z)-7-Oxozeaenol, a small-molecule inhibitor of TAK1, we show that caspase-8 activation during TAK1 inhibition results in cleavage of bo...
35 CitationsSource
#1Beiyun C. Liu (Tufts University)H-Index: 6
#2Joseph Sarhan (Tufts University)H-Index: 3
Last.Alexander Poltorak (Tufts University)H-Index: 18
view all 9 authors...
Summary Legionella pneumophila elicits caspase-11-driven macrophage pyroptosis through guanylate-binding proteins (GBPs) encoded on chromosome 3. It has been proposed that microbe-driven IFN upregulates GBPs to facilitate pathogen vacuole rupture and bacteriolysis preceding caspase-11 activation. We show here that macrophage death occurred independently of microbial-induced IFN signaling and that GBPs are dispensable for pathogen vacuole rupture. Instead, the host-intrinsic IFN status sustained ...
19 CitationsSource
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