A systems analysis identifies a feedforward inflammatory circuit leading to lethal influenza infection


Autoria(s): Brandes, Marlène; Klauschen, Frederick; Kuchen, Stefan; Germain, Ronald N.
Data(s)

03/07/2013

Resumo

For acutely lethal influenza infections, the relative pathogenic contributions of direct viral damage to lung epithelium versus dysregulated immunity remain unresolved. Here, we take a top-down systems approach to this question. Multigene transcriptional signatures from infected lungs suggested that elevated activation of inflammatory signaling networks distinguished lethal from sublethal infections. Flow cytometry and gene expression analysis involving isolated cell subpopulations from infected lungs showed that neutrophil influx largely accounted for the predictive transcriptional signature. Automated imaging analysis, together with these gene expression and flow data, identified a chemokine-driven feedforward circuit involving proinflammatory neutrophils potently driven by poorly contained lethal viruses. Consistent with these data, attenuation, but not ablation, of the neutrophil-driven response increased survival without changing viral spread. These findings establish the primacy of damaging innate inflammation in at least some forms of influenza-induced lethality and provide a roadmap for the systematic dissection of infection-associated pathology.

Formato

application/pdf

Identificador

http://boris.unibe.ch/43234/1/%2CDanaInfo%3D.aadBhpxEjlwJn0z%2B1-s2.0-S0092867413007150-main.pdf

Brandes, Marlène; Klauschen, Frederick; Kuchen, Stefan; Germain, Ronald N. (2013). A systems analysis identifies a feedforward inflammatory circuit leading to lethal influenza infection. Cell, 154(1), pp. 197-212. Cell Press 10.1016/j.cell.2013.06.013 <http://dx.doi.org/10.1016/j.cell.2013.06.013>

doi:10.7892/boris.43234

info:doi:10.1016/j.cell.2013.06.013

info:pmid:23827683

urn:issn:0092-8674

Idioma(s)

eng

Publicador

Cell Press

Relação

http://boris.unibe.ch/43234/

Direitos

info:eu-repo/semantics/restrictedAccess

Fonte

Brandes, Marlène; Klauschen, Frederick; Kuchen, Stefan; Germain, Ronald N. (2013). A systems analysis identifies a feedforward inflammatory circuit leading to lethal influenza infection. Cell, 154(1), pp. 197-212. Cell Press 10.1016/j.cell.2013.06.013 <http://dx.doi.org/10.1016/j.cell.2013.06.013>

Palavras-Chave #610 Medicine & health #570 Life sciences; biology
Tipo

info:eu-repo/semantics/article

info:eu-repo/semantics/publishedVersion

PeerReviewed