lta4h MO Knockdown Results in Increased Susceptibility to Mm
(A) Representative fluorescence images of control (top) and lta4h morphant (bottom) fish 5 dpi with 173 bacteria. The scale bar represents 200 μm.
(B) Mean bacterial loads per embryo for control (wt) and lta4h morphant embryos at 1.5 and 6 dpi with 150 bacteria (n = 4 groups of 5 animals for each time point). Error bars represent the SD.
(C) Survival of control and lta4h morphant fish mock-injected or injected with 177 bacteria (n = 25 per group). Hazard Ratio for death of infected morphants = 9.0, p < 0.0001 (Kaplan Meier method with log-rank [Mantel-Cox] test). Data representative of three independent experiments.
(D) Fluorescence image of non-cording bacteria within a granuloma in control animals (top) and cording bacteria in lta4h morphant (bottom) at 5 dpi with infection dose of 150 bacteria. The scale bar represents 20 μm.
(E) Mean proportion of animals with cording in three independent groups of 15–40 animals 4 dpi with 173 bacteria. p = 0.003 (Student′s unpaired t test). Error bars represent the standard error of the mean (SEM).
(F) Bacterial burden at 5 dpi as determined by fluorescence pixel counts (FPC) for vehicle-treated or 100 μM bestatin-treated animals after injection with ∼150 CFU Mm. p = 0.03 (Student′s unpaired t test).
(G) Fluorescence image of non-cording bacteria within a granuloma in control animals (top) and cording bacteria in animals treated with 100 μM bestatin (bottom) at 5 dpi as described in (F). The scale bar represents 10 μm.
(H) Quantitation of cording at 4 dpi in five independent groups of 10–30 animals treated with vehicle or 100 μM bestatin after injection with 100–200 CFU Mm. p = 0.007 (Student′s unpaired t test). Error bars represent the SEM.
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Reprinted from Cell, 140(5), Tobin, D.M., Vary, J.C. Jr, Ray, J.P., Walsh, G.S., Dunstan, S.J., Bang, N.D., Hagge, D.A., Khadge, S., King, M.C., Hawn, T.R., Moens, C.B., and Ramakrishnan, L., The lta4h Locus Modulates Susceptibility to Mycobacterial Infection in Zebrafish and Humans, 717-730, Copyright
(2010) with permission from Elsevier.
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