Investigation of Tuberculosis Infection in Monkeys: Evaluation of Drug, Protein, and Lipid Localization in Tissue Samples using Imaging Mass Spectrometry

摘要

RIF was readily detected in most tissues, however due to the generally small sample size and lack of surrounding unaffected lung, the overall pattern of distribution is difficult to assess. INH showed no apparent localization to the granulomas and significant animal-to-animal variability was observed. Several proteins and lipids showed granuloma-specific localization patterns. Proteins at m/z 3446, 3741 and 10,823 were more abundant in granulomas, while m/z 4046 and10,092 were mostly absent and m/z 8451 was present in a ring around the granulomas. Similarly, PC (16:0/16:0) was less intense in the granulomas, while PC (38:4) was present in a ring around the lesions. These molecular distributions are consistent with the cellular microenvironment in this disease: many granulomas have a center of caseous necrosis surrounded by cellular regions (ring) containing more immune cells, lymphocytes, and macrophages.