Figure 2. Internalization of single large aggregates is more cytotoxic than several smaller aggregates.
(A) Fraction of dead MDM after phagocytosing one large aggregate of Mtb (black line) or multiple small aggregates (red line) with a similar cumulative sum of Mtb to the single internalizations, but with all aggregates being smaller than 50 bacilli each. The frequency of cell death was 47% for multiple internalizations (n = 47) and 71% for single internalizations (n = 62, p=5×10−4 by bootstrap). Individual cell fates are shown in (B) for cells internalizing multiple small aggregates, and (C) for cells internalizing a similar number of Mtb as single aggregates. The blue circles are internalizations of aggregates of 10 or fewer Mtb, red circles are clumps of 11–49 Mtb, and black circles are 50–81 Mtb. Line color changes from green to dark blue at time of death. Stars indicate internalizations of dead infected cells. An equal number of cells is shown in (B) and (C) to facilitate comparison. Mean number of Mtb phagocytosed was 49.6 ± 18.9 for MDM internalizing multiple small Mtb clumps, and 49.4 ± 14.3 for MDM internalizing a single large clump.