Fig. 2: Rv0884c/d-serine impairs anti-TB immunity.
a, In vitro growth curve of Rv0884c_cKDTet incubated with or without ATc under aeration or hypoxia at 37 °C for 14 days. b, In vitro growth curve of H37Rv with addition of 10 mM d-serine incubated under aeration (left) or hypoxia (right) at 37 °C for 14 days. c–f, C57BL/6 mice were aerosol-infected with ~200 c.f.u. per mouse of Rv0884c_cKDTet with or without ATc, Rv0884c_cKDTet with ATc and d-serine, Rv0884c_cKDTet+Rv0884c (F108A) with ATc, and Rv0884c_cKDTet+Rv0884c with ATc. After 4 weeks of infection, histopathology of lung sections from infected mice was assessed via H&E staining (c; scale bar, 200 μm (top) and 100 μm (bottom)), histology score (d), acid-fast staining (e; scale bar, 20 μm (top) and 10 μm (bottom)) and bacterial load (f). The areas of leucocyte infiltration between conditions are labelled using yellow dotted circles. g–j, C57BL/6 mice were aerosol-infected with ~200 c.f.u. per mouse of H37Rv, and then 30 g l−1 d-serine was administered via drinking water to half of the infected mice. After 4 weeks of infection, histopathology of lung sections from infected mice was assessed via H&E staining (g; scale bar, 200 μm (top) and 100 μm (bottom)), histology score (h), acid-fast staining (i; scale bar, 20 μm (top) and 10 μm (bottom)) and bacterial load (j). The areas of leucocyte infiltration between conditions are labelled using yellow dashed circles. Data in a–j represent one experiment with at least three independent biological replicates. Results are shown as mean ± s.e.m. Two-way ANOVA with Tukey’s multiple comparisons test (a,b), one-way ANOVA with Tukey’s multiple comparisons test (d,f) and two-tailed unpaired Student’s t-test (h,j) were used for statistical analysis.
