Infection of human monocyte-derived dendritic cells by ANDES Hantavirus enhances pro-inflammatory state, the secretion of active MMP-9 and indirectly enhances endothelial permeability

Simple item page
dc.contributor.authorMarsac, Delphine
dc.contributor.authorGarcía, Stephanie
dc.contributor.authorPino, Karla
dc.contributor.authorFerrés Garrido, Marcela Viviana
dc.contributor.authorLópez Lastra, Marcelo Andrés
dc.contributor.authorKalergis Parra, Alexis Mikes
dc.contributor.authorFournet, Alexandra
dc.contributor.authorAguirre, Adam
dc.contributor.authorVeas, Francisco
dc.date.accessioned2019-10-17T13:57:57Z
dc.date.available2019-10-17T13:57:57Z
dc.date.issued2011
dc.date.updated2019-10-14T18:51:00Z
dc.description.abstractAbstract Background Andes virus (ANDV), a rodent-borne Hantavirus, is the major etiological agent of Hantavirus cardiopulmonary syndrome (HCPS) in South America, which is mainly characterized by a vascular leakage with high rate of fatal outcomes for infected patients. Currently, neither specific therapy nor vaccines are available against this pathogen. ANDV infects both dendritic and epithelial cells, but in despite that the severity of the disease directly correlates with the viral RNA load, considerable evidence suggests that immune mechanisms rather than direct viral cytopathology are responsible for plasma leakage in HCPS. Here, we assessed the possible effect of soluble factors, induced in viral-activated DCs, on endothelial permeability. Activated immune cells, including DC, secrete gelatinolytic matrix metalloproteases (gMMP-2 and -9) that modulate the vascular permeability for their trafficking. Methods A clinical ANDES isolate was used to infect DC derived from primary PBMC. Maturation and pro-inflammatory phenotypes of ANDES-infected DC were assessed by studying the expression of receptors, cytokines and active gMMP-9, as well as some of their functional status. The ANDES-infected DC supernatants were assessed for their capacity to enhance a monolayer endothelial permeability using primary human vascular endothelial cells (HUVEC). Results Here, we show that in vitro primary DCs infected by a clinical isolate of ANDV shed virus RNA and proteins, suggesting a competent viral replication in these cells. Moreover, this infection induces an enhanced expression of soluble pro-inflammatory factors, including TNF-α and the active gMMP-9, as well as a decreased expression of anti-inflammatory cytokines, such as IL-10 and TGF-β. These viral activated cells are less sensitive to apoptosis. Moreover, supernatants from ANDV-infected DCs were able to indirectly enhance the permeability of a monolayer of primary HUVEC. Conclusions Primary human DCs, that are primarily targeted by hantaviruses can productively be infected by ANDV and subsequently induce direct effects favoring a proinflammatory phenotype of infected DCs. Finally, based on our observations, we hypothesize that soluble factors secreted in ANDV-infected DC supernatants, importantly contribute to the endothelial permeability enhancement that characterize the HCPS.
dc.fuente.origenBiomed Central
dc.identifier.citationVirology Journal. 2011 May 13;8(1):223
dc.identifier.doi10.1186/1743-422X-8-223
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/26660
dc.issue.numeroNo. 223
dc.language.isoen
dc.pagina.final9
dc.pagina.inicio1
dc.revistaVirology Journal volumees_ES
dc.rightsacceso restringido
dc.rights.holderMarsac et al; licensee BioMed Central Ltd.
dc.subject.ddc610
dc.subject.deweyMedicina y saludes_ES
dc.subject.otherSíndrome pulmonar por hantaviruses_ES
dc.subject.otherInfecciones por hantavirus - Chilees_ES
dc.subject.otherInfecciones por hantavirus - Chile -Terapiaes_ES
dc.titleInfection of human monocyte-derived dendritic cells by ANDES Hantavirus enhances pro-inflammatory state, the secretion of active MMP-9 and indirectly enhances endothelial permeabilityes_ES
dc.typeartículo
dc.volumenVol. 8
sipa.codpersvinculados146335
sipa.codpersvinculados66180
sipa.codpersvinculados84823
sipa.codpersvinculados90610
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
12985_2011_Article_1310.pdf
Size:
914.79 KB
Format:
Adobe Portable Document Format
Description:
Download
License bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
license.txt
Size:
0 B
Format:
Item-specific license agreed upon to submission
Description:
Download
Collections
Artículos de revistas