Figure 1.
Effects of ATRA treatment on MDSCs and Pc infection in mice.
Immunosuppressed, Pc-infected mice were treated with vehicle control 8% DMSO, ATRA, or TMP-SMX for 3, 4, and 5 weeks as indicated in the figure. Treatment was initiated 3 weeks after Pc inoculation. (A) Giemsa-stained BAL cells cytospun on slides. Red arrows indicate MDSC-like cells, and blue arrows denote alveolar macrophages. (B) Representative flow cytograms of BAL cells from mice in each group at each time point. The percentage of Gr-1+/CD11b+ cells in each sample is shown in the right upper quadrant of each flow cytogram. (C) Percentage of Gr-1+/CD11b+ cells in BALF, as determined by flow cytometry. Data are means ± S. D. of 3–6 mice in each group at each time point. (D) Histologic sections of the lungs stained with GMS (left) and H&E (right). Red arrows indicate GMS-stained Pc organisms. Images are representative of 3–6 mice in each group at each time point. Microscope magnification: 40X.
Figure 2.
Effects of ATRA-PMQ combination on MDSCs and Pc infection in mice.
Immunosuppressed, Pc-infected mice were given vehicle control 8% DMSO, ATRA-PMQ, or TMP-SMX for 2 weeks. Treatment was initiated 3 weeks after Pc inoculation. (A) Lung impression smear stained with Giemsa. Red arrows indicate nuclei of Pc organisms. Magnification: 100X. (B) Giemsa-stained BAL cells cytospun on slides. Black arrows indicate MDSC-like cells. Microscope magnification: 40X. Images are representative of 3–6 mice of each group.
Figure 3.
Effects of ATRA, ATRA-PMQ, and TMP-SMX on MDSCs in rats.
Immunosuppressed, Pc-infected rats were given vehicle control 8% DMSO, ATRA, ATRA-PMQ, or TMP-SMX for 4 weeks. Treatment was initiated 2 weeks after Pc inoculation. BAL cells were examined by flow cytometry. The percentage of His48+/CD11bc+ MDSCs in each sample is shown in the right upper quadrant of each flow cytogram.
Figure 4.
Increased number of CD11c+ BAL cells after ATRA, ATRA-PMQ, or TMP-SMX treatment.
Immunosuppressed, Pc-infected mice were given vehicle control 8% DMSO, ATRA, ATRA-PMQ, or TMP-SMX for 5 weeks. Treatment was initiated 3 weeks after Pc inoculation. BAL cells were collected and analyzed by flow cytometry with fluorescence labeled anti-mouse CD11c antibody. (A) Representative flow cytograms of BAL cells from animals of each group. (B) Percentage of CD11c+ BAL cells in BALF, as determined by flow cytometry. Data are means ± S. D. of 3–6 mice in each group.
Figure 5.
No relapse of PcP after cessation of ATRA-PMQ treatment.
Immunosuppressed, Pc-infected mice were treated with ATRA-PMQ or TMP-SMX for 2 weeks and then examined for the presence of Pc at 3 weeks after initiation of treatment and at 3 weeks after cessation of the three-week treatment. Lung tissues were subjected to Pc mitochondrial rRNA PCR, and the PCR products were electrophoresed on a 1% agarose gel.
Figure 6.
Survival curves of PcP rats treated with DMSO, ATRA-PMQ, or TMP-SMX.
Animals were sacrificed when agonal or when the study was concluded. The percentage of animals survived on each day is plotted. Results are from 10 animals of each condition.