Eicosanoid Profile of Influenza A Virus Infected Pigs

Abstract

Respiratory tract infections caused by the Influenza A virus (IAV) are a worldwide problem for human and animal health. Within this study, we analyzed the impact of IAV infection on the immune-related lipidome (eicosanoids) of the pig as new infection model. For this purpose, we performed HPLC-MS/MS using dynamic multiple reaction monitoring and analyzed lung, spleen, blood plasma and bronchoalveolar lavages. IAV infection leads to collective changes in the levels of the analyzed hydroxyeicosatrienoic acids (HETEs), hydroxydocosahexaenoic acids (HDHAs) and epoxyeicosatrienoic acids (EETs), and moreover, unique eicosanoid changes in several sample types, even under mild infection conditions. In accordance with different mouse infection studies, we observed infection-related patterns for 12-HETE, 15-HETE and 17-HDHA, which seem to be common for IAV infection. Using a long-term approach of 21 days we established an experimental setup that can be used also for bacterial-viral coinfection experiments.

Keywords: Influenza A virus; eicosanoids; infection; lipid mediator; pig.

Figure 1

Heatmap displaying fold changes (infection/control) of all measured eicosanoid amounts of all sample types and time points. Decreased levels are shown in green, increased amounts in red and comparable amounts in black. Grey fields: below detection limit.

Figure 2

Overview of significant changed amounts of eicosanoids during infection in the spleen (A) and the lung (B) per g sample; the BALF per 5 mL (C) and blood plasma per mL (D). Asterisks indicate significant changes (p-value ≤ 0.05) using Mann-Whitney U test for control (n = 3 for tissue and BALF, and n at least 6 for plasma) and infection (n = 5 for tissue and BALF, and n at least 6 for plasma). The following color pattern was used: control (black), 4 dpi (orange), 7 dpi (red) and 21 dpi (brown) for A–C. For plasma (D) control samples for all days were illustrated in black and plasma samples from infected animals were shown for 0 dpi (grey), 2 dpi (light orange), 4 dpi (orange), 7 dpi (red) and 14 dpi (dark red).