Reinfection promotes sterilizing immunity in secondary strain granulomas and restricts thoracic lymph node dissemination.

(a) The bacterial burdens (CFU) of all granulomas in naïve macaques (blue), or reinfection macaques (library A: gray; library B: red; library A and B: red/gray circles) 4 weeks post-Mtb library B challenge. The CFU for all granulomas in the reinfected macaques were significantly reduced relative to the naïve monkeys. N = 42 ranging from 2 to 20 per animal (naïve) and N = 94 ranging from 5 to 32 per animal (reinfection). Each symbol is a granuloma, p < .0001, Mann-Whitney test. (b) Total bacterial genome counts (CEQ) and viable bacterial burden counts (CFU) were determined from the same Library B granulomas from naïve or reinfection macaques and bacterial killing (CFU/CEQ) for each granuloma shown in (c), p = 0.0002, Mann-Whitney test. Each symbol for (b) and (c) is a granuloma. CFU was significantly lower than CEQ in both naïve and reinfection granulomas (b), paired t-tests, p-values reported in figure. Both CEQ and CFU were reduced in reinfection granulomas compared with granulomas from naïve animals (b), Mann-Whitney tests, p-values reported in figure. (d) There was no correlation between extent of host lung inflammation (total lung FDG activity) and bacterial killing (CFU/CEQ) of library B granulomas (Spearman r = 0.38, p = 0.2454). In b, N = 12 (naïve) and N = 21 (reinfection). In b and c, N = 12 (naïve) and N = 11 (reinfection).