The TLR4 antagonist Eritoran protects mice from lethal influenza infection Kari Ann Shirey, Wendy...

The TLR4 antagonist Eritoran protects mice from lethal influenza infection

 Kari Ann Shirey, Wendy Lai, Alison J. Scott, Michael Lipsky, Pragnesh Mistry, Lioubov M. Pletneva, Christopher L. Karp,

Jaclyn McAlees, Theresa L. Gioannini, Jerrold Weiss, Wilbur H. Chen, Robert K. Ernst, Daniel P. Rossignol, Fabian Gusovsky,

Jorge C. G. Blanco & Stefanie N. Vogel.

Nature 23 May 2013 volume 497 p498-502.

Shirey Kari Ann et al. (2013) Fig. Suppl. 8

Model

Shirey Kari Ann et al. (2013) Fig. 1a

Infection Protocol

Shirey Kari Ann et al. (2013) Fig. 1b

Survival of PR8 (Influenza virus) –infected C57BL mice.

Nhu QM et al. (2010) Novel signaling interactions between proteinase-activated receptor 2 and Toll-like receptors in vitro and in vivo. Mucosal Immunity 3, 29-30.

Figure 7c

Shirey Kari Ann et al. (2013) Fig. 1b

Shirey Kari Ann et al. (2013) Fig. Suppl. 1a

Shirey Kari Ann et al. (2013) Fig. Suupl. 1b

Eritoran-mediated protection Is overcome by increased PR8 challenge doses.

Shirey Kari Ann et al. (2013) Fig. Suppl. 1c

Infection with human pandemic influenza A/California/07/2009 H1N.

Shirey Kari Ann et al. (2013) Fig. 1c

Survival when Eritoran treatment starts 2, 4, and 6 days p.i.

Shirey Kari Ann et al. (2013) Fig. 2a

Mock PR8 untreated

PR8 + E5564

(80% of sections) (20% of sections)

Shirey Kari Ann et al. (2013) Fig. 2b

Pathology score of PR8 infection in C57Bl mice.

Puls-Oxymetry mouse pup.

Shirey Kari Ann et al. (2013) Fig. 2c

Pulse-Oxymetry of PR8 infected C57Bl mice.

Sigmodon hispididus or Cotton rat.

Shirey Kari Ann et al. (2013) Fig. 2d

Uninfected + E5564 H3N2 H3N2 + E5564

Lung pathology of H3N2 in cotton rats.

Shirey Kari Ann et al. (2013) Fig. 2e

Lung Pathology of H3N2 infection in cotton rats.

Shirey Kari Ann et al. (2013) Fig. 3

Lung viral titers after PR8 infection.

Calculate TCID50.

Shirey Kari Ann et al. (2013) Suppl. Table 1

Shirey Kari Ann et al. (2013) Fig. Suppl. 2

Measuring DNA amplification:Every cycle releases 2 molecules of the Reporter Fluorophore from their quencher;Fluorescence measures the number of amplification cycles.

qRT- PCR

Shirey Kari Ann et al. (2013) Fig. 4a

Tumor Necrosis Factor a Interleukin-1b

Prostaglandin endoperoxide synthase 2= Cyclo-oxygenase 2

Chemotaxin CXCL1 = MIP1

PR8-induced cytokine production in mice lungs.

Shirey Kari Ann et al. (2013) Fig. Suppl. 3a

PR8-induced cytokine production in mice lungs.

Shirey Kari Ann et al. (2013) Fig. Suppl. 3b

Shirey Kari Ann et al. (2013) Fig. 4b

H3N2 induced cytokine production in cotton rat lungs.

Shirey Kari Ann et al. (2013) Fig. Suppl. 4

Shirey Kari Ann et al. (2013) Fig. 5a

Shirey Kari Ann et al. (2013) Fig. 5b

Shirey Kari Ann et al. (2013) Fig. Suppl. 5.

Shirey Kari Ann et al. (2013) Fig. Suppl. 6

(Palmitoic Acid)3 Cysteine Serine (lysine)4 is a specific agonist of TLR-2

Figure. OxPLs of diverse origin competitively inhibit the binding of LPS to LBP, CD14, and MD2, the soluble and cell-associated proteins that confer LPS sensitivity on the

transmembrane signaling component TLR4.

Erridge C Arterioscler Thromb Vasc Biol 2009;29:337-338Copyright © American Heart Association

Shirey Kari Ann et al. (2013) Fig. Suppl. 7

1-palmitoyl- 2- linoleyl phospho choline

1- palmitoyl- 2- arachidonoyl phospho choline

1-palmitoyl-2 (9-oxo) nonanoyl phosphocholine

1-palmitoyl- 2- expoxy-sisoprostane E2 phospho choline

Shirey Kari Ann et al. (2013) Fig. Suppl. 7

Shirey Kari Ann et al. (2013) Fig. Suppl. 8

Shirey Kari Ann et al. (2013) Fig. 1a