Figure 7.

iNOS and caspase-8 influence the host response to SARS-CoV-2, but only caspase-8 impacts hemophagocytic lymphohistiocytosis (HLH) disease severity

(A and B) Rectal temperatures of (A) wild-type (WT, n = 12), Ripk3^−/− (n = 6), Casp8^−/−Ripk3^−/− (n = 10), and Tnf^−/−Fasl^gld/gldTrail^−/− (n = 6) mice, or (B) WT (n = 14) and Nos2^−/− (n = 12) mice injected with PolyI:C (10 mg/kg) for 24 h followed by LPS (5 mg/kg) to induce HLH-like disease.

(C) Cleaved caspase-3 immunohistochemistry of endpoint small intestine sections taken from mice treated as described (A and B). Each image represents a separate mouse. Positive cells are indicated with red arrows. Scale bar, 100 μm.

(D and E) Endpoint plasma TNF, IL-1β and IL-6 concentrations of mice treated as described in (D) A and (E) B.

(F and G) (F) TCID50 infectious units per lung and (G) percentage weight loss of WT (n = 22), Nos2^+/− (n = 18) or Nos2^−/− (n = 20) mice infected with 1.5 × 10⁷ TCID50 infectious units of SARS-CoV-2 for three days.

(H and I) (H) TCID50 infectious units per lung and (I) percentage weight loss of WT (n = 21), Mlkl^−/− (n = 23), Casp8^+/−Mlkl^−/− (n = 17), or Casp8^−/−Mlkl^−/− (n = 15) mice infected with 1.5 × 10⁷ TCID50 infectious units of SARS-CoV-2 for three days.

Data represent the mean value ± SEM pooled from at least 2 independent experimental cohorts of mice. p > 0.05 (n.s.), p ≤ 0.05 (^∗), p ≤ 0.01 (^∗∗), p ≤ 0.001 (^∗∗∗), p ≤ 0.0001 (^∗∗∗∗).