As part of a study to investigate early changes following exposure to aerosols of Mycobacterium tuberculosis (Mtb), 10 rhesus macaques ( Macaca mulatta) were infected with high (731 colony forming units [cfu]), medium (70cfu) or low (7cfu) doses of Mtb, and tissues were examined at 2 and 3 weeks post infection (wpi). Clinical disease was not observed. Results of advanced imaging and pathological findings were compared with respect to the delivered dose and time post infection. Magnetic resonance imaging revealed lesions in the lungs at these early time points exvivo immediately prior to detailed post-mortem examination in the absence of clinical disease. In animals exposed to high and medium doses of Mtb that were studied at 2 and 3wpi, a range of lesions includingsmall foci of mainly mononuclear cells, primarily macrophages (granulomatous lesions), as well as obvious granulomas, were observed microscopically in the lungs, including lymphatics and hilar lymph nodes. In the low-dose group at 3 weeks, small lesions were identified in the lung and hilar lymph nodes of one animal, and the remaining two animals in this group had lesions in either lung or hilar lymph node. Acid fast bacilli were demonstrated in the lung and lymph nodes in all animals that received high and medium doses, and the lymph nodes of two animals at the low dose. A dose-dependent effect was observed with increasing dose and time post infection. Furthermore, early dissemination of bacilli to the draining, hilar lymph nodes with concomitant granulomatous lesion formation was observed. By contributing to the recognition of early lesion development due to aerosol challenge of Mtb in the rhesus macaque, this study forms a basis for further investigation of early lesions and may inform the design of future vaccine and therapeutic studies involving early time points in this species.
Bibliographical noteFunding Information:
This work was supported by the Department of Health, UK . The views expressed in this publication are those of the authors and not necessarily those of the Department of Health. We thank staff of the Biological Investigations Group, HPA, for assistance in conducting the studies; A. White for ESR determinations; and K. Hatch, L. Hunter and M. Howarth for expert technical assistance.
Copyright 2013 Elsevier B.V., All rights reserved.
- Early granuloma