Abstract

To re-evaluate virulence of Mycobacterium tuberculosis (M. tb) in cattle, we experimentally infected calves with M. tb andMycobacterium bovisvia intratracheal injection at a dose of 2.0×107 CFU and observed the animals for 33 weeks. The intradermal tuberculin test and IFN-γin vitro release assay showed that both M. tb and M. bovis induced similar responses. Immunohistochemical staining of pulmonary lymph nodes indicated that the antigen MPB83 of both M. tb and M. bovis were similarly distributed in the tissue samples. Histological examinations showed all of the infected groups exhibited neutrophil infiltration to similar extents. Although the infected cattle did not develop granulomatous inflammation, the metabolic profiles changed significantly, which were characterized by a change in energy production pathways and increased concentrations of N-acetyl glycoproteins. Glycolysis was induced in the infected cattle by decreased glucose and increased lactate content, and enhanced fatty acid β-oxidation was induced by decreased TG content, and decreased gluconeogenesis indicated by the decreased concentration of glucogenic and ketogenic amino acids promoted utilization of substances other than glucose as energy sources. In addition, an increase in acute phase reactive serum glycoproteins, together with neutrophil infiltration and increased of IL-1β production indicated an early inflammatory response before granuloma formation. In conclusion, this study indicated that both M. tb and M.bovis were virulent to cattle. Therefore, it is likely that cattle with M. tb infections would be critical to tuberculosis transmission from cattle to humans. Nuclear magnetic resonance was demonstrated to be an efficient method to systematically evaluate M. tb and M. bovi sinfection in cattle.

Highlights

  • Tuberculosis (TB) is one of the most contagious human diseases

  • M. bovis is the main pathogen of bovine TB (BTB) and can cause TB in a wide range of animal hosts as well as humans

  • At week 10 PI, most of the infected calves were PPDpositive with ratios of positive calves in the M. tbH37Rv, M. tb1458, and M. bovis groups of 10/10, 7/10, and 9/10 respectively, which were higher than those of PPD-positive calves detected at week 16 PI

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Summary

Introduction

Tuberculosis (TB) is one of the most contagious human diseases. In 2011, there were an estimated 8.7 million new TB cases globally, resulting in approximately 1.4 million deaths [1]. The top 22 countries with high TB-burden account for approximately 81.6% of all new TB cases arising each year [2] Most of these high TB-burden countries are developing countries [2], which have experienced the great economical losses due to bovine TB (BTB) in cattle caused by a reduction in animal productivity as well as losses in domestic and international trade in addition to the cost of control and eradication programs [3]. The proportion of human TB cases due to M. bovis in most developing countries remains largely unknown, it was speculated that the TB bacillus could account for as many as 10–15% of new human TB cases occurring in those countries [4] depending on the regions, patterns of cattle farming and trade, implementation of BTB control or eradication programs, and regional economic status, etc. The proportion of human TB cases due to M. bovis in most developing countries remains largely unknown, it was speculated that the TB bacillus could account for as many as 10–15% of new human TB cases occurring in those countries [4] depending on the regions, patterns of cattle farming and trade, implementation of BTB control or eradication programs, and regional economic status, etc. [5,6]

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