Histologic characterization and localization of Borrelia burgdorferi within doxycycline and untreated rhesus macaques with late disseminated Lyme disease. A: Heart (IH22 doxycycline treated); mild multifocal lymphoplasmacytic interstitial inflammation. B: Visceral pericardium (IH22 doxycycline treated); localized mild lymphoplasmacytic inflammation. C: Heart (IK14 doxycycline treated); red fluorescence of a morphologically intact spirochete within myocardial interstitium; differential interference contrast (DIC) image applied to enhance contrast. D: Skeletal muscle (IK66 doxycycline treated); mild localized lymphoplasmacytic interstitial inflammation. E–G: Red, green, and merged images illustrate localized interstitial fluorescence within the skeletal muscle (IK66); DIC image applied to enhance contrast. E: Three-dimensional imaging reveals the cylindrical morphologic features of the dual-stained specimen, with the DIC partially removed, indicating that this is a cross section of a spirochete; 1 unit = 6.17 μm. F: DIC added back to the three-dimensional rotated view. G: Red, green, and merged immunofluorescent staining of B. burgdorferi within the tissue. H: Stifle synovium (IH11 doxycycline treated); mild lymphoplasmacytic inflammation infiltrating hyperplastic synovial epithelium. I: Stifle perisynovial adipose tissue (IL09 doxycycline treated); minimal localized lymphoplasmacytic perivascular cuffing. J: Localized red fluorescence in perisynovial adipose tissue (IL09 doxycycline treated). Three-dimensional imaging in inset shows cylindrical shape of the structure, indicating that this may be a cross section of the spirochete; 1 unit = 6.17 μm. DIC image applied to enhance contrast. K: Urinary bladder; the lamina propria is infiltrated by mild lymphoplasmacytic inflammation. L: Urinary bladder; a discrete lymphoid nodule expands the lamina propria. M: Red fluorescent staining reveals an object with spirochete morphologic features and/or associated antigen within the lamina propria of the urinary bladder (IL75 untreated). Scale bars: 20 μm (C and M); 10 μm (E–G, and J). Original magnification: ×10 (A, B, D, H, I, K, and L); ×63 (additional ×2 amplification applied with Leica LAS X software; C).