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Hantavirus-induced disruption of the endothelial barrier: neutrophils are on the payroll.

Schönrich G, Krüger DH, Raftery MJ - Front Microbiol (2015)

Bottom Line: Hantaviruses infect endothelial cell layers in vitro without causing any cytopathogenic effect and without increasing permeability.This implies that the mechanisms underlying vascular hyperpermeability in hantavirus-associated disease are more complex and that immune mechanisms play an important role.In this review we highlight the latest developments in hantavirus-induced immunopathogenesis.

View Article: PubMed Central - PubMed

Affiliation: Institute of Medical Virology, Helmut-Ruska-Haus, Charité-Universitätsmedizin Berlin , Berlin, Germany.

ABSTRACT
Viral hemorrhagic fever caused by hantaviruses is an emerging infectious disease for which suitable treatments are not available. In order to improve this situation a better understanding of hantaviral pathogenesis is urgently required. Hantaviruses infect endothelial cell layers in vitro without causing any cytopathogenic effect and without increasing permeability. This implies that the mechanisms underlying vascular hyperpermeability in hantavirus-associated disease are more complex and that immune mechanisms play an important role. In this review we highlight the latest developments in hantavirus-induced immunopathogenesis. A possible contribution of neutrophils has been neglected so far. For this reason, we place special emphasis on the pathogenic role of neutrophils in disrupting the endothelial barrier.

No MeSH data available.


Related in: MedlinePlus

Proposed immune mechanisms contributing to hantavirus-induced disruption of the endothelial barrier. Both cellular and humoral components of innate and adaptive immune responses could contribute to vascular leakage of hantavirus-infected vessels. In response to hantavirus-infected EC, neutrophils generate NETs or may secrete inflammatory cytokines such as TNF-α which directly or indirectly increase vascular permeability. The humoral pattern recognition receptor PTX3 and antibodies activate complement. Activated complement components induce cytoskeletal rearrangements in EC further increasing dysfunction of the EC barrier. NK cells may kill bystander EC or also secrete TNF-α. DC may carry the virus from lung tissue to EC of the microvasculature in various organs or become infected after interaction with virus-infected EC. As hantavirus-infected DC mature they migrate to draining lymph nodes to initiate a vigorous CD8+ T cell response. The latter could contribute to vascular leakage by direct killing of hantavirus-infected EC or, more likely, by releasing TNF-α.
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Figure 2: Proposed immune mechanisms contributing to hantavirus-induced disruption of the endothelial barrier. Both cellular and humoral components of innate and adaptive immune responses could contribute to vascular leakage of hantavirus-infected vessels. In response to hantavirus-infected EC, neutrophils generate NETs or may secrete inflammatory cytokines such as TNF-α which directly or indirectly increase vascular permeability. The humoral pattern recognition receptor PTX3 and antibodies activate complement. Activated complement components induce cytoskeletal rearrangements in EC further increasing dysfunction of the EC barrier. NK cells may kill bystander EC or also secrete TNF-α. DC may carry the virus from lung tissue to EC of the microvasculature in various organs or become infected after interaction with virus-infected EC. As hantavirus-infected DC mature they migrate to draining lymph nodes to initiate a vigorous CD8+ T cell response. The latter could contribute to vascular leakage by direct killing of hantavirus-infected EC or, more likely, by releasing TNF-α.

Mentions: Humoral as well as cellular mechanisms of the adaptive and innate immune system contribute to hantavirus-induced disruption of the endothelial barrier (Figure 2). Intriguingly, neutrophils which so far have not been regarded as a player in hantavirus-induced immunopathogenesis seem to be important. NETs as well as neutrophil-derived factors such as VEGF, PTX3, and TNF-α can cause vascular dysfunction. Further studies are needed to reveal whether strategies aiming at neutrophil function can prevent hantavirus-induced immunopathogenesis. Furthermore, it is possible that NETs and other neutrophil-derived mediators of vascular hyperpermeability play a role in VHF caused by members of other virus families.


Hantavirus-induced disruption of the endothelial barrier: neutrophils are on the payroll.

Schönrich G, Krüger DH, Raftery MJ - Front Microbiol (2015)

Proposed immune mechanisms contributing to hantavirus-induced disruption of the endothelial barrier. Both cellular and humoral components of innate and adaptive immune responses could contribute to vascular leakage of hantavirus-infected vessels. In response to hantavirus-infected EC, neutrophils generate NETs or may secrete inflammatory cytokines such as TNF-α which directly or indirectly increase vascular permeability. The humoral pattern recognition receptor PTX3 and antibodies activate complement. Activated complement components induce cytoskeletal rearrangements in EC further increasing dysfunction of the EC barrier. NK cells may kill bystander EC or also secrete TNF-α. DC may carry the virus from lung tissue to EC of the microvasculature in various organs or become infected after interaction with virus-infected EC. As hantavirus-infected DC mature they migrate to draining lymph nodes to initiate a vigorous CD8+ T cell response. The latter could contribute to vascular leakage by direct killing of hantavirus-infected EC or, more likely, by releasing TNF-α.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4373389&req=5

Figure 2: Proposed immune mechanisms contributing to hantavirus-induced disruption of the endothelial barrier. Both cellular and humoral components of innate and adaptive immune responses could contribute to vascular leakage of hantavirus-infected vessels. In response to hantavirus-infected EC, neutrophils generate NETs or may secrete inflammatory cytokines such as TNF-α which directly or indirectly increase vascular permeability. The humoral pattern recognition receptor PTX3 and antibodies activate complement. Activated complement components induce cytoskeletal rearrangements in EC further increasing dysfunction of the EC barrier. NK cells may kill bystander EC or also secrete TNF-α. DC may carry the virus from lung tissue to EC of the microvasculature in various organs or become infected after interaction with virus-infected EC. As hantavirus-infected DC mature they migrate to draining lymph nodes to initiate a vigorous CD8+ T cell response. The latter could contribute to vascular leakage by direct killing of hantavirus-infected EC or, more likely, by releasing TNF-α.
Mentions: Humoral as well as cellular mechanisms of the adaptive and innate immune system contribute to hantavirus-induced disruption of the endothelial barrier (Figure 2). Intriguingly, neutrophils which so far have not been regarded as a player in hantavirus-induced immunopathogenesis seem to be important. NETs as well as neutrophil-derived factors such as VEGF, PTX3, and TNF-α can cause vascular dysfunction. Further studies are needed to reveal whether strategies aiming at neutrophil function can prevent hantavirus-induced immunopathogenesis. Furthermore, it is possible that NETs and other neutrophil-derived mediators of vascular hyperpermeability play a role in VHF caused by members of other virus families.

Bottom Line: Hantaviruses infect endothelial cell layers in vitro without causing any cytopathogenic effect and without increasing permeability.This implies that the mechanisms underlying vascular hyperpermeability in hantavirus-associated disease are more complex and that immune mechanisms play an important role.In this review we highlight the latest developments in hantavirus-induced immunopathogenesis.

View Article: PubMed Central - PubMed

Affiliation: Institute of Medical Virology, Helmut-Ruska-Haus, Charité-Universitätsmedizin Berlin , Berlin, Germany.

ABSTRACT
Viral hemorrhagic fever caused by hantaviruses is an emerging infectious disease for which suitable treatments are not available. In order to improve this situation a better understanding of hantaviral pathogenesis is urgently required. Hantaviruses infect endothelial cell layers in vitro without causing any cytopathogenic effect and without increasing permeability. This implies that the mechanisms underlying vascular hyperpermeability in hantavirus-associated disease are more complex and that immune mechanisms play an important role. In this review we highlight the latest developments in hantavirus-induced immunopathogenesis. A possible contribution of neutrophils has been neglected so far. For this reason, we place special emphasis on the pathogenic role of neutrophils in disrupting the endothelial barrier.

No MeSH data available.


Related in: MedlinePlus