Figure 1
Distinct outcomes of self-limited versus non resolving P. aeruginosa lung infection. (a) Number of living bacteria in BAL and lungs from mice infected with ∼3.5 × 106 CFU/mouse of planktonic or agar-embedded RP73. Total airway bacterial load was determined as the sum of the CFU found in BAL and lung suspensions upon serial dilution, spreading onto TSA, and o.n. growth. (b, c) Total and differential leukocyte counts in BAL from infected mice. c shows mathematical resolution indices: Ψmax, maximum PMN number; Tmax, time of Ψmax; Ψ50, 50% decrease in PMN number; T50, time for Ψ50; Ri, resolution interval (T50–Tmax); TPMN=Mono/MΦ, time of equivalence of PMN and monocytes/MΦ. (d) Weight changes in mice receiving i.t. inoculum of RP73-laden agar beads (∼3.5 × 106 CFU/mouse) and relative total leukocytes (e), PMN, and monocyte/MΦ (f) number in BAL at the indicated time point following challenge with agar-enmeshed RP73. (g) Histopathology of lung microsections during chronic RP73 infection. Photomicrographs are representative from 4–10 mice/data point. (h) Levels of LTB4 and the biogenic precursor of RvD1 17-HDoHE in lung homogenates at early and late phase of chronic RP73 infection. Amount of each lipid mediator was determined by taking into account the total homogenate volume. Results are mean±s.e.m. from 3 independent experiments with 15 mice. The lower panel shows a representative multiple reaction monitoring MS/MS spectrum of 17-HDoHE identified by the LC-MS/MS diagnostic ions indicated in Table 2. (i) Levels of select cytokines and chemokines in lung homogenates during RP73 chronic infection. *P<0.05; **P=0.005, ***P<0.001 vs. uninfected mice. Results are mean±s.e.m. from 2 (panels A-C) or 3 (d–h) independent experiments with 4 (0, 3, 5 DPI) or 10 mice (1, 7, 14, 21 DPI)/data point. Results in panel I are mean±s.e.m. from three independent experiments with three (0 DPI) and five (5 and 21 DPI) mice/group.
