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. 2015 Jan 20;4:e04494. doi: 10.7554/eLife.04494

Figure 5. MHV68 latency rescues HOIL-1 KO, IL-6, Caspase-1 and Caspase-1;Caspase-11-deficient mice from Listeria-induced lethality.

(A) Survival of control (blue symbols; mock n = 9, MHV68 n = 15) and HOIL-1 KO (red symbols; mock n = 10, MHV68 n = 20) mice challenged with 106 CFU Listeria 28 days following mock infection (circles) or infection with 106 PFU MHV68 (squares). *p ≤ 0.0083; logrank Mantel–Cox test corrected for multiple comparisons. (B) Survival of control (blue symbols) and HOIL-1 KO (red symbols) mice challenged with 106 CFU Listeria 28 days following intranasal mock infection (circles) or infection with 5 × 104 PFU wild-type (squares) or ORF73.stop (triangles) MHV68. Significantly different groups were: control mock infected and control MHV68wt infected, control mock infected and HOIL-1 KO MHV68wt infected, control mock infected and HOIL-1 KO MHV68orf73.stop infected, HOIL-1 KO mock infected and control MHV68wt infected, HOIL-1 KO mock infected and HOIL-1 KO MHV68wt infected, control MHV68wt infected and control MHV68orf73.stop infected, control MHV68wt infected and HOIL-1 KO MHV68orf73.stop infected, HOIL-1 KO MHV68wt infected and control MHV68orf73.stop infected, HOIL-1 KO MHV68wt infected and HOIL-1 KO MHV68orf73.stop infected, control MHV68orf73.stop infected and HOIL-1 KO MHV68orf73.stop infected. *p ≤ 0.0033; logrank Mantel–Cox test corrected for multiple comparisons. (C) Cytokine transcript levels in peritoneal cells from mock (circles) and MHV68-infected (squares) control (blue symbols) and HOIL-1 KO (red symbols) mice (28 days post-infection). (D) Induction of cytokine transcripts in peritoneal cells from mock (circles) and MHV68-infected (squares) control (blue symbols) and HOIL-1 KO (red symbols) mice (28 days) 3 hr after infection with 105 Listeria. Each symbol represents an individual mouse. For (C) and (D), *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001, ****p ≤ 0.0001. Statistical analyses were performed using one-way ANOVA. (E) Survival of control (blue symbols) and Il6−/− (purple symbols) mice challenged with 106 CFU Listeria 28 days following mock infection (circles) or infection with 106 PFU MHV68 (squares). *p ≤ 0.0083; logrank Mantel–Cox test corrected for multiple comparisons. (F) Survival of control (blue symbols), Caspase-1;Caspase-11 (orange symbols) and Caspase-1 (green symbols) –deficient mice challenged with 106 CFU Listeria 28 days following mock infection (circles) or infection with 106 PFU MHV68 (squares). *p ≤ 0.0033; logrank Mantel–Cox test corrected for multiple comparisons.

DOI: http://dx.doi.org/10.7554/eLife.04494.019

Figure 5.

Figure 5—figure supplement 1. MHV68 latency-induced cross-protection is maintained for at least 6 months.

Figure 5—figure supplement 1.

Survival of control (blue symbols) and HOIL-1 KO (red symbols) mice challenged with 106 CFU Listeria 6 months after mock infection (circles) or infection with 106 PFU MHV68 (squares). Statistical analyses were performed by logrank Mantel–Cox test corrected for multiple comparisons, with p ≤ 0.0083 considered significant. Control mock vs HOIL-1 KO mock, p = 0.1824; control mock vs control MHV68 infected, p = 0.0408; control mock vs HOIL-1 KO MHV68 infected, p = 0.0070; HOIL-1 KO mock vs control MHV68 infected, p = 0.0028; HOIL-1 KO mock vs HOIL-1 KO MHV68 infected, p = 0.0003; control MHV68 infected vs HOIL-1 KO MHV68 infected, p = 0.9303.
Figure 5—figure supplement 2. MHV68 latency enhances the listericidal activity of peritoneal macrophages.

Figure 5—figure supplement 2.

Listeria CFU in control (blue symbols) and HOIL-1 KO (red symbols) ex vivo cultures of peritoneal macrophages from mock (circles) or MHV68-infected (32 days, squares) mice at 0 and 6 hr post-infection. Data are combined from two independent experiments. Each symbol represents an individual mouse analyzed in duplicate. Cells from the same mouse were used for both 0 hr and 6 hr time points. Statistical analyses were performed by one-way ANOVA with Holm-Sidak's multiple comparison test for each time point.
Figure 5—figure supplement 3. Il6−/− mice have increased susceptibility to Listeria infection.

Figure 5—figure supplement 3.

Survival of control (blue circles) and Il6−/− (purple squares) mice following i.p. inoculation with 105 CFU Listeria. *p ≤ 0.0083; logrank Mantel–Cox test corrected for multiple comparisons.