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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 neutrophil-mediated mechanisms contributing to vascular leakage during hantavirus infection. Neutrophils are activated through virus-induced β2 integrin signaling. Activated platelets also stimulate neutrophils through β2 integrins. Depending on the β2 integrin ligands involved and possibly further microenvironmental stimuli neutrophils can be activated in a different way resulting in (A) NETosis or (B) secretion of inflammatory cytokines such as TNF-α or VEGF. In both cases increased vascular leakage is generated, although most likely by distinct mechanisms.
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Figure 1: Proposed neutrophil-mediated mechanisms contributing to vascular leakage during hantavirus infection. Neutrophils are activated through virus-induced β2 integrin signaling. Activated platelets also stimulate neutrophils through β2 integrins. Depending on the β2 integrin ligands involved and possibly further microenvironmental stimuli neutrophils can be activated in a different way resulting in (A) NETosis or (B) secretion of inflammatory cytokines such as TNF-α or VEGF. In both cases increased vascular leakage is generated, although most likely by distinct mechanisms.

Mentions: Neutrophils express β2 integrins, i.e., β2αL (CD18/CD11a), β2αM (CD18/CD11b) and β2αX (CD18/CD11c; Langereis, 2013). A recent study has demonstrated that hantaviruses strongly activate neutrophils through β2 integrin signaling resulting in NETosis (Raftery et al., 2014). In addition, activated platelets recruit neutrophils rapidly to the site of inflamed EC during VHF. Subsequently, platelet-leukocyte aggregation is mediated by the interaction of platelet proteins with β2 integrins on neutrophils (Zapata et al., 2014). Several infection models have demonstrated that platelet-neutrophil interactions through β2 integrins result also in NETosis (Clark et al., 2007; Caudrillier et al., 2012; McDonald et al., 2012; Jenne et al., 2013). Thus, β2 integrins may act as a master switch of NETosis during VHF (Figure 1A).


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

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

Proposed neutrophil-mediated mechanisms contributing to vascular leakage during hantavirus infection. Neutrophils are activated through virus-induced β2 integrin signaling. Activated platelets also stimulate neutrophils through β2 integrins. Depending on the β2 integrin ligands involved and possibly further microenvironmental stimuli neutrophils can be activated in a different way resulting in (A) NETosis or (B) secretion of inflammatory cytokines such as TNF-α or VEGF. In both cases increased vascular leakage is generated, although most likely by distinct mechanisms.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: Proposed neutrophil-mediated mechanisms contributing to vascular leakage during hantavirus infection. Neutrophils are activated through virus-induced β2 integrin signaling. Activated platelets also stimulate neutrophils through β2 integrins. Depending on the β2 integrin ligands involved and possibly further microenvironmental stimuli neutrophils can be activated in a different way resulting in (A) NETosis or (B) secretion of inflammatory cytokines such as TNF-α or VEGF. In both cases increased vascular leakage is generated, although most likely by distinct mechanisms.
Mentions: Neutrophils express β2 integrins, i.e., β2αL (CD18/CD11a), β2αM (CD18/CD11b) and β2αX (CD18/CD11c; Langereis, 2013). A recent study has demonstrated that hantaviruses strongly activate neutrophils through β2 integrin signaling resulting in NETosis (Raftery et al., 2014). In addition, activated platelets recruit neutrophils rapidly to the site of inflamed EC during VHF. Subsequently, platelet-leukocyte aggregation is mediated by the interaction of platelet proteins with β2 integrins on neutrophils (Zapata et al., 2014). Several infection models have demonstrated that platelet-neutrophil interactions through β2 integrins result also in NETosis (Clark et al., 2007; Caudrillier et al., 2012; McDonald et al., 2012; Jenne et al., 2013). Thus, β2 integrins may act as a master switch of NETosis during VHF (Figure 1A).

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