<i>Y</i><i>ersinia pestis</i>targets neutrophils via complement receptor 3

Merritt, Peter M.; Nero, Thomas; Bohman, Lesley; Felek, Suleyman; Krukonis, Eric S.; Marketon, Melanie M.

doi:10.1111/cmi.12391

Cited by 20 publications

(18 citation statements)

References 92 publications

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“…For example, contact between the Y. pseudotuberculosis adhesive protein invasin and β1 integrin receptor on neutrophils induces extrusion of microbicidal DNA, via NETosis, a processes that is inhibited by effectors delivered by the T3SS (Figure 1A) [23]. In addition to stimulating host immune responses, adhesion of yersiniae to host cells facilitates Yop effector translocation by the T3SS into immune cells during infection, while factors in serum can restrict levels of translocation by shifting the specificity of Yop targeting [24–26]. Additional bacterial factors are important for fine-tuning effector translocation.…”

Section: Later Interactions Of Yersinia With Host Cells-important Formentioning

confidence: 99%

Yersinia versus host immunity: how a pathogen evades or triggers a protective response

Chung

Bliska

2016

Current Opinion in Microbiology

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The human pathogenic Yersinia species cause diseases that represent a significant source of morbidity and mortality. Despite this, specific mechanisms underlying Yersinia pathogenesis and protective host responses remain poorly understood. Recent studies have shown that Yersinia disrupt cell death pathways, perturb inflammatory processes and exploit immune cells to promote disease. The ensuing host responses following Yersinia infection include coordination of innate and adaptive immune responses in an attempt to control bacterial replication. Here, we highlight current advances in our understanding of the interactions between the pathogenic yersiniae and host cells, as well as the protective host responses mobilized to counteract these pathogens. Together, these studies enhance our understanding of Yersinia pathogenesis and highlight the ongoing battle between host and microbe.

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Section: Later Interactions Of Yersinia With Host Cells-important Formentioning

confidence: 99%

Yersinia versus host immunity: how a pathogen evades or triggers a protective response

Chung

Bliska

2016

Current Opinion in Microbiology

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“…Our assays detect factor H binding at high concentrations of Y. pestis , which may indicate that Ail‐dependent recruitment of factor H in buboes may prevent production of the alarmones, C3a and C5a, thus preventing PMN infiltration. Alternatively, it is possible that the lack of PMN recruitment seen during bubonic plague models of infection are due to a reduced efficiency of Yop delivery via T3SS in a Δ ail mutant (Marketon et al ., ; Merritt et al ., ). Nonetheless, our studies show Y. pestis can survive complement‐mediated lysis in human serum, even without the ability to recruit factor H or vitronectin (as demonstrated by Ail‐F80A/F130A).…”

Section: Discussionmentioning

confidence: 97%

Ail provides multiple mechanisms of serum resistance to Yersinia pestis

Thomson

Plecha

Krukonis

2018

Molecular Microbiology

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SUMMARY Ail, a multifunctional outer membrane protein of Yersinia pestis, confers cell binding, Yop delivery, and serum resistance activities. Resistance to complement proteins in serum is critical for survival of Y. pestis during the septicemic stage of plague infections. Bacteria employ a variety of tactics to evade the complement system, including recruitment of complement regulatory factors, such as factor H, C4b-binding protein (C4BP), and vitronectin (Vn). Y. pestis Ail interacts with the regulatory factors Vn and C4BP, and Ail homologs from Y. enterocolitica and Y. pseudotuberculosis recruit factor H. Using co-sedimentation assays, we demonstrate that two surface-exposed amino acids, F80 and F130, are required for interaction of Y. pestis Ail with Vn, factor H, and C4BP. However, although Ail-F80A/F130A fails to interact with these complement regulatory proteins, it still confers 10,000-fold more serum resistance than a Δail strain and prevents C9 polymerization, potentially by directly interfering with MAC assembly. Using site-directed mutagenesis we further defined this additional mechanism of complement evasion conferred by Ail. Finally, we find that at Y. pestis concentrations reflective of early-stage septicemic plague, Ail weakly recruits Vn and fails to recruit factor H, suggesting that this alternative mechanism of serum resistance may be essential during plague infection.

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“…While recent studies have indicated that Ail influences in vivo target cell selection for Yop delivery during Yersinia infections (33)(34)(35), the mechanism(s) by which Ail directs cell targeting of Yop secretion is unclear. Ail could recruit ECM components to direct Yop delivery to specific immune cells with receptors for those components to disarm the host immune response.…”

Section: Discussionmentioning

confidence: 99%

Defining the Ail Ligand-Binding Surface: Hydrophobic Residues in Two Extracellular Loops Mediate Cell and Extracellular Matrix Binding To Facilitate Yop Delivery

et al. 2017

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Yersinia pestis, the causative agent of plague, binds host cells to deliver cytotoxic Yop proteins into the cytoplasm that prevent phagocytosis and generation of proinflammatory cytokines. Ail is an eight-stranded β-barrel outer membrane protein with four extracellular loops that mediates cell binding and resistance to human serum. Following the deletion of each of the four extracellular loops that potentially interact with host cells, the Ail-Δloop 2 and Ail-Δloop 3 mutant proteins had no cell-binding activity while Ail-Δloop 4 maintained cell binding (the Ail-Δloop 1 protein was unstable). Using the codon mutagenesis scheme SWIM (selection without isolation of mutants), we identified individual residues in loops 1, 2, and 3 that contribute to host cell binding. While several residues contributed to the binding of host cells and purified fibronectin and laminin, as well as Yop delivery, three mutations, F80A (loop 2), S128A (loop 3), and F130A (loop 3), produced particularly severe defects in cell binding. Combining these mutations led to an even greater reduction in cell binding and severely impaired Yop delivery with only a slight defect in serum resistance. These findings demonstrate that Y. pestis Ail uses multiple extracellular loops to interact with substrates important for adhesion via polyvalent hydrophobic interactions.

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Yersinia pestistargets neutrophils via complement receptor 3

Cited by 20 publications

References 92 publications

Yersinia versus host immunity: how a pathogen evades or triggers a protective response

Yersinia versus host immunity: how a pathogen evades or triggers a protective response

Ail provides multiple mechanisms of serum resistance to Yersinia pestis

Defining the Ail Ligand-Binding Surface: Hydrophobic Residues in Two Extracellular Loops Mediate Cell and Extracellular Matrix Binding To Facilitate Yop Delivery

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