Figure - PMC

Skip to main content

An official website of the United States government

Here's how you know

Here's how you know

Official websites use .gov
A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS
A lock ( ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

View full-text article in PMC

. 2022 Jul 21;11(1):1790–1805. doi: 10.1080/22221751.2022.2095930

Search in PMC
Search in PubMed
View in NLM Catalog
Add to search

© 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

PMC Copyright notice

graphic file with name TEMI_A_2095930_F0007a_OC.jpg — Adjunctive ZOL/IL-2 (Group-2) or IL-2 (Group-3) administration after MDR-Mtb infection and TB drug treatment led to milder MDR-TB pathology/lesions compared to TB drugs alone and saline controls. (A) Shown are representative digital images of whole lungs obtained at end time points for individual MDR-TB-macaques in 4 studied groups, with animal ID displayed in the upper-left corner. The vertical/horizontal bars at the bottom left represent the 1-cm scale derived from the fluorescence rulers of each original photo, including the sliced sections. Large red arrows indicate diffuse haemorrhages with tubercle lesions; white arrows denote gross tubercle lesions; pink arrows show mid-size haemorrhage changes; small black arrows point to focal gross tubercle lesions. All macaques in saline group exhibited typical severe TB tubercles as shown, whereas representative changes were displayed for other groups. (B). Representative digital images of the cut-sections of the right caudal lung lobes from 3 representative MDR-Mtb V791-infected macaques in each of four groups, with the ID numbers indicated in the upper-left corner. Note that the lung lobes of MDR-Mtb-infected macaques were sliced into exhibition sections, because more stringent safety protocols had to be adhered in the setting of MDR-Mtb infection. TB lesions could be adjudged based on the examples indicated by the various colour arrows: large black arrows demonstrated the presence of caseation TB pneumonia or extensive coalescing TB granulomas; large red arrows point to the diffuse haemorrhage with coalescing TB tubercules/lesions; large pink arrows indicate diffuse haemorrhage changes without coalescing tubercles; white arrows indicate coalescing TB tubercles; small pink arrows denote focal haemorrhages; small black arrows point to the small noncoalescing TB granulomas lesions. (C). Graph data of mean gross pathology scores ± SEM for 4 groups of MDR-Mtb-infected macaques (n = 6). The scores were calculated as we previously described [7,22]. Statistical analysis was done using ANOVA test, with p values indicated for comparisons between groups. (D)–(E). Representative histopathological images of H&E-stained lung sections in the right caudal lobes collected from representative MDR-Mtb-infected macaques in 4 studied groups. The upper and lower panels showed 50× (D) and 200× (E) magnifications, respectively, for different right caudal lung lobe sections of 3 representative macaques in each of 4 studied groups. Overall, the sections from the saline group of macaques exhibited severe TB lesions (large black arrows) and different stages of haemorrhagic changes (large red arrows). The recent haemorrhages displayed residual erythrocytes/debris or pigment haemoglobin; earlier haemorrhage appeared to be predominated by post-haemorrhage necrosis or destruction. The severe TB lesions (such as WPA20, WPA21) were characterized by widespread necrosis and tissue destruction, with many epithelioid cells, macrophages, and degenerative or necrotic cells found in the edges or centres of the tubercles. There was less-sufficient infiltration of lymphocytes. Most lung sections from three Group-1 macaques (Drug alone) exhibited histopathology of haemorrhages (red arrows) or necrotic granulomas (black arrows), although less necrotic or focal granulomas were also seen. In contrast, ZOL/IL2-treated (Group-2) and IL2-treated (Group-3) macaques generally showed small non-necrotic or less-necrotic granulomas, and localized or contained by large numbers of lymphocytes as pointed by small black arrows. The unbiased processes for collecting tissues for histopathology were performed as we previously described [7,22].

graphic file with name TEMI_A_2095930_F0007b_OC.jpg — Adjunctive ZOL/IL-2 (Group-2) or IL-2 (Group-3) administration after MDR-Mtb infection and TB drug treatment led to milder MDR-TB pathology/lesions compared to TB drugs alone and saline controls. (A) Shown are representative digital images of whole lungs obtained at end time points for individual MDR-TB-macaques in 4 studied groups, with animal ID displayed in the upper-left corner. The vertical/horizontal bars at the bottom left represent the 1-cm scale derived from the fluorescence rulers of each original photo, including the sliced sections. Large red arrows indicate diffuse haemorrhages with tubercle lesions; white arrows denote gross tubercle lesions; pink arrows show mid-size haemorrhage changes; small black arrows point to focal gross tubercle lesions. All macaques in saline group exhibited typical severe TB tubercles as shown, whereas representative changes were displayed for other groups. (B). Representative digital images of the cut-sections of the right caudal lung lobes from 3 representative MDR-Mtb V791-infected macaques in each of four groups, with the ID numbers indicated in the upper-left corner. Note that the lung lobes of MDR-Mtb-infected macaques were sliced into exhibition sections, because more stringent safety protocols had to be adhered in the setting of MDR-Mtb infection. TB lesions could be adjudged based on the examples indicated by the various colour arrows: large black arrows demonstrated the presence of caseation TB pneumonia or extensive coalescing TB granulomas; large red arrows point to the diffuse haemorrhage with coalescing TB tubercules/lesions; large pink arrows indicate diffuse haemorrhage changes without coalescing tubercles; white arrows indicate coalescing TB tubercles; small pink arrows denote focal haemorrhages; small black arrows point to the small noncoalescing TB granulomas lesions. (C). Graph data of mean gross pathology scores ± SEM for 4 groups of MDR-Mtb-infected macaques (n = 6). The scores were calculated as we previously described [7,22]. Statistical analysis was done using ANOVA test, with p values indicated for comparisons between groups. (D)–(E). Representative histopathological images of H&E-stained lung sections in the right caudal lobes collected from representative MDR-Mtb-infected macaques in 4 studied groups. The upper and lower panels showed 50× (D) and 200× (E) magnifications, respectively, for different right caudal lung lobe sections of 3 representative macaques in each of 4 studied groups. Overall, the sections from the saline group of macaques exhibited severe TB lesions (large black arrows) and different stages of haemorrhagic changes (large red arrows). The recent haemorrhages displayed residual erythrocytes/debris or pigment haemoglobin; earlier haemorrhage appeared to be predominated by post-haemorrhage necrosis or destruction. The severe TB lesions (such as WPA20, WPA21) were characterized by widespread necrosis and tissue destruction, with many epithelioid cells, macrophages, and degenerative or necrotic cells found in the edges or centres of the tubercles. There was less-sufficient infiltration of lymphocytes. Most lung sections from three Group-1 macaques (Drug alone) exhibited histopathology of haemorrhages (red arrows) or necrotic granulomas (black arrows), although less necrotic or focal granulomas were also seen. In contrast, ZOL/IL2-treated (Group-2) and IL2-treated (Group-3) macaques generally showed small non-necrotic or less-necrotic granulomas, and localized or contained by large numbers of lymphocytes as pointed by small black arrows. The unbiased processes for collecting tissues for histopathology were performed as we previously described [7,22].