Reduced pathological damage in lungs and spleens of guinea pigs infected with H37Rv upon AZD0530 treatment. Reduced pathological damage in lungs and spleens.

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Reduced pathological damage in lungs and spleens of guinea pigs infected with H37Rv upon AZD0530 treatment. Reduced pathological damage in lungs and spleens of guinea pigs infected with H37Rv upon AZD0530 treatment. After 8 weeks of treatment, the lung and spleen tissues of the test animals were harvested and subjected to histopathological analyses. (A) Lung tissue from an untreated animal with granulomatous lesions (black arrows) is shown here. (B) Low-power photomicrograph (×40) of this lung tissue shows multiple granulomas in the lung parenchyma. (C) High-power photomicrograph (×100) showing the cellular composition in one of the granulomas. A central zone of necrosis surrounded by epithelioid cells can be observed. (D) The lung tissue from a treated animal showing lesser granulomatous lesions (black arrows). (E and F) No necrotic zones were observed in the granulomas at ×40 (E) and ×100 (F) magnifications. (G) Plot representing number of granulomas (necrotizing and nonnecrotizing) counted in lung sections from treated and untreated animals. The blue lines represent the average value for the untreated or treated sets of animals. (H) A section of spleen from an untreated animal at ×100 magnification is shown here. A large granuloma with central necrosis in the white pulp of the spleen can be observed (N). (I) High-power photomicrograph (×400) from the granuloma shows necrosis (N) in the upper half of the image with epithelioid cells in the lower half. (J) Spleens from the treated animals had no granulomatous lesions. A section of spleen from a treated animal showing normal splenic parenchyma is presented here at ×100 magnification. (K) High-power photomicrograph (×400) of the same section shows a portion of a lymphoid follicle in the white pulp. (L) Plot representing number of granulomas (necrotizing and nonnecrotizing) counted in the spleen sections from treated and untreated animals. The blue lines represent the average values for the untreated or treated sets of animals. (M) Splenomegaly was observed in infected guinea pigs that did not receive AZD0530 treatment (bar, 1 cm). G, granuloma; N, necrosis; E, epithelioid cells; AS, alveolar space; RP, red pulp; WP, white pulp; FC, follicular center. The images depicted here are stained with hematoxylin and eosin. (N) Phosphorylation of IκBα in H37Rv-infected THP-1 macrophages that were either untreated or treated with AZD0530 (20 µM) at 48 h postinfection. Pallavi Chandra et al. mSphere 2016; doi:10.1128/mSphere.00043-15