Figure 1.
Effect of leptin receptor function on the survival, the degree of lung injury and inflammation during influenza A infection.
db/db and C57BL/6 mice were inoculated with influenza A virus (A/WSN/33 [H1N1]) (a) 1500 pfu/mouse or (b) 500 pfu/mouse and mortality was subsequently assessed on a daily basis. Percentage of weight loss was also followed daily for the mice infected with (c) 1500 pfu/mouse or (d) 500 pfu/mouse. Four days after infection with influenza A virus 1500 pfu/mouse, db/db and C57BL/6 mice underwent a bronchoalveolar lavage for (e) assessment of cell count, (f) total protein, (g,h) inflammatory cytokines, (i) flow cytometry, and (j) the assessment of lung pathology (Hematoxylin and Eosin staining). * p<0.05 compared to PBS control. ** p<0.05 db/db compared to wild-type mice.
Figure 2.
Effect of leptin receptor function on viral replication.
Plaque forming units (pfu) were counted in MDCK cells treated with lung homogenates from db/db and C57BL/6 mice infected with influenza A virus (a) 1500 pfu/mouse on Day 4 and (b) 500 pfu/mouse on Day 2 and Day 4. We also measured (c) interferon-α (IFN- α) levels in BALF in wild-type and db/db mice 2 days after infection with influenza A virus (1500 pfu/mouse).
Figure 3.
Effect of the leptin receptor function specifically within lung epithelium and within macrophages and neutrophils on survival, lung injury, and inflammation during influenza A infection.
(a) Representative images and (b) weights of db/db, LepRfl/fl, SP-C-Cre+/+/LepRfl/fl, and LysM-Cre+/+/LepRfl/fl mice are shown. Quantitative real-time PCR reveals appropriate knockout of the leptin receptor (c) within the macrophages in LysM-Cre+/+/LepRfl/fl mice and (d) within the lung epithelium in SP-C-Cre+/+/LepRfl/fl mice. LepRfl/fl, SP-C-Cre+/+/LepRfl/fl, and LysM-Cre+/+/LepRfl/fl mice were inoculated with influenza A virus (500 pfu/mouse) with assessment of (e) mortality and (f) daily weight. Four days after infection with influenza A virus (500 pfu/mouse), LepRfl/fl, SP-C-Cre+/+/LepRfl/fl, and LysM-Cre+/+/LepRfl/fl mice underwent bronchoalveolar lavage for levels of (g) cell count, (h) total protein, (i–k) inflammatory cytokines and (l) lung pathology (Hematoxylin and Eosin staining).
Figure 4.
Effect of leptin receptor function specifically within lung epithelium and within macrophages and neutrophils on viral replication.
Plaque forming units (pfu) were counted in MDCK cells treated with lung homogenates from LepRfl/fl, SP-C-Cre+/+/LepRfl/fl, and LysM-Cre+/+/LepRfl/fl mice infected with Influenza A virus 500 pfu/mouse on Day 2 and Day 4. * p<0.05 LysM-Cre+/+/LepRfl/fl and SP-C-Cre+/+/LepRfl/fl mice compared to LepRfl/fl mice.