Stephen C. Bunnell
Tufts University
T-cell receptorImmunologyT cellBiologyCell biology
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Publications 45
#1Giang T. Nguyen (Tufts University)H-Index: 1
#2Lamyaa Shaban (Tufts University)H-Index: 3
Last. Joan Mecsas (Tufts University)H-Index: 34
view all 7 authors...
Klebsiella pneumoniae is a respiratory, blood, liver, and bladder pathogen of significant clinical concern. We show that the adaptor protein, SKAP2, is required for protection against K. pneumoniae (ATCC 43816) pulmonary infections. Skap2-/- mice had 100-fold higher bacterial burden when compared to wild-type and burden was controlled by SKAP2 expression in innate immune cells. Skap2-/- neutrophils and monocytes were present in infected lungs, and the neutrophils degranulated normally in respons...
#1Michael Fray (Tufts University)H-Index: 2
#2John C. Charpentier (University of Massachusetts Boston)
Last. Stephen C. Bunnell (Tufts University)H-Index: 18
view all 5 authors...
Vav family guanine nucleotide exchange factors (GEFs) are essential regulators of immune function. Despite their structural similarity, Vav1 promotes and Vav2 opposes T cell receptor (TCR)-induced calcium entry. Using a Vav1-deficient Jurkat T cell line, we find that Vav1 facilitates calcium entry via non-catalytic scaffolding functions that are encoded by the catalytic core of Vav1 and flanking linker regions. We implicate in this scaffolding function a previously undescribed polybasic motif th...
#1Elizabeth A. DeRiso (Tufts University)
#2Andrea L. Szymczak-Workman (University of Pittsburgh)H-Index: 1
Last. Stephen C. Bunnell (Tufts University)H-Index: 18
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The NF-{kappa}B essential modulator protein (NEMO) is required for activation of canonical NF-{kappa}B by the T cell antigen receptor (TCR). However, the subcellular localization of NEMO during this process is not well understood. By dynamically imaging fluorescent NEMO chimeras in live human T cells, we demonstrate that NEMO is rapidly recruited into TCR microclusters via domains previously implicated in the recognition of linear and K63-linked polyubiquitin. The recruitment of NEMO into TCR mi...
#1Parisa Kalantari (Tufts University)H-Index: 1
#2Stephen C. Bunnell (Tufts University)H-Index: 18
Last. Miguel J. Stadecker (Tufts University)H-Index: 39
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Schistosomiasis is a major helminthic disease in which damage to the affected organs is orchestrated by a pathogenic host CD4 T helper (Th) cell-mediated immune response against parasite eggs. In the case of the species Schistosoma mansoni, the resulting granulomatous inflammation and fibrosis takes place in the liver and intestines. The magnitude of disease varies greatly from individual to individual but in a minority of patients there is severe disease and death. S. mansoni infection in a mur...
#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
#1Juliana B. Lewis (Tufts University)H-Index: 1
#2Frank A. Scangarello (Tufts University)H-Index: 1
Last. Stephen C. Bunnell (Tufts University)H-Index: 18
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Antigen recognition by the T cell receptor (TCR) directs the assembly of essential signaling complexes known as SLP-76 microclusters. Here, we show that the interaction of the adhesion and degranulation-promoting adaptor protein (ADAP) with SLP-76 enables the formation of persistent microclusters and the stabilization of T cell contacts, promotes integrin-independent adhesion, and enables the upregulation of CD69. Using point mutants and a novel phospho-specific antibody, we show that Y595 is es...
1 CitationsSource
#1Maria A. DeCicco RePass (Tufts University)H-Index: 2
#2Najma Bhat (Tufts Medical Center)H-Index: 6
Last. Honorine D. Ward (Tufts University)H-Index: 42
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Abstract Cryptosporidium spp. are the causative agents of diarrheal disease worldwide, but effective treatments are lacking. Cryptosporidium employs mucin-like glycoproteins with O-glycans to attach to and infect host intestinal epithelial cells. The Tn antigen (GalNAcα1-Ser/Thr) is an O-glycan essential for these processes, as Tn-specific lectins and a Tn-specific monoclonal antibody block attachment to and infection of host cells in vitro. The enzymes in Cryptosporidium catalyzing their synthe...
2 CitationsSource
#1Parisa Kalantari (Tufts University)H-Index: 1
#2Yoelkys Morales (Tufts University)H-Index: 1
Last. Miguel J. Stadecker (Tufts University)H-Index: 39
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Summary The immunopathology caused by schistosome helminths varies greatly in humans and among mouse strains. A severe form of parasite egg-induced hepatic granulomatous inflammation, seen in CBA mice, is driven by Th17 cells stimulated by IL-1β and IL-23 produced by dendritic cells that express CD209a (SIGNR5), a C-type lectin receptor (CLR) related to human DC-SIGN. Here, we show that CD209a-deficient CBA mice display decreased Th17 responses and are protected from severe immunopathology. In v...
5 CitationsSource
#1Tess L. Killpack (Wellesley College)H-Index: 3
#2Maria Ballesteros (Tufts University)H-Index: 1
Last. Tanja Petnicki-Ocwieja (Tufts University)H-Index: 12
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3 CitationsSource
#1Tanja Petnicki-Ocwieja (Tufts University)H-Index: 12
#2Aurélie Kern (Tufts University)H-Index: 7
Last. Linden T. Hu (Tufts University)H-Index: 33
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Innate immune engagement results in the activation of host defenses that produce microbe-specific inflammatory responses. A long-standing interest in the field of innate immunity is to understand how varied host responses are generated through the signaling of just a limited number of receptors. Recently, intracellular trafficking and compartmental partitioning have been identified as mechanisms that provide signaling specificity for receptors by regulating signaling platform assembly. We show t...
7 CitationsSource