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Enhanced tissue damage following H1N1 infection in human precision-cut lung slices (PCLS)

 
: Danov, Olga; Martin, Gaël; Greif, A.; Bailly, B.; Braubach, Peter; Jonigk, Danny; Warnecke, Gregor; Itzstein, M. von; Sewald, Katherina; Wronski, Sabine; Braun, Armin

American Journal of Respiratory and Critical Care Medicine 199 (2019), Abstract A5742
ISSN: 1073-449X
ISSN: 0003-0805
ISSN: 1535-4970
American Thoracic Society (ATS International Conference) <2019, Dallas/Tex.>
English
Abstract
Fraunhofer ITEM ()

Abstract
Annual seasonal epidemics with Influenza A virus (IAV) strains result in 3-5 million severe cases in children and elderly individuals. Therefore, in this study the immune response of lower respiratory tract tissue to H1N1 (California/04/2009) pandemic strain was compared to seasonal H3N2 (Perth/16/2009) in viable human precision-cut lung slices (PCLS) ex vivo. PCLS were inoculated with 104-106 ffu /mL for 1 h and incubated 48 h post infection. Local immune response was measured with MSD, tissue damage observed by LDH release and immunofluorescence staining showed virus localization. Human tissue showed a dose-dependent immune response to IAV with key cytokine secretion for interferon response with IFN-α/β/γ/λ, IP-10, T-cell response by secretion of I-TAC and IL-2 and pro-inflammatory response with IL-6 and MIP-1α. Although both strains induced comparable and strong anti-viral response in lung tissue ex vivo, cytolytic tissue damage was only observed for the pandemic strain. Virus localization showed a spot like infection throughout PCLS. This study shows that human local immune response is similar to seasonal and pandemic strain however the pandemic strain induced higher tissue damage. The ex vivo infected lung tissue will be used for efficacy testing of novel anti-viral drugs. Here, we demonstrate the efficacy of Zanamivir in influenza infection.

: http://publica.fraunhofer.de/documents/N-565330.html