Oral Presentation International Veterinary Immunology Symposium 2016

Systemic monocyte/macrophage changes in response to mycobacterial infection. (#79)

Shyamala Thirunavukkarasu 1 , Kumudika de Silva 2 3 , Hilary Connors 2 3 , Chad Cooper 2 3 , Douglas J Begg 2 3 , Auriol C Purdie 2 3 , Richard J Whittington 2 3 , Karren M Plain 2 3
  1. Health Science Center, University of Tennessee, Memphis, Tennessee, US
  2. University of Sydney, Camden, NSW, Australia
  3. Faculty of Veterinary Science,School of Life and Environmental Sciences, University of Sydney, Camden, NSW, Australia

Mycobacterial infections in livestock animals are a welfare concern as well as causing substantial economic losses to the industry. Mycobacterium avium subspecies paratuberculosis (MAP) is a highly adapted and resistant pathogen that causes Johne’s disease in sheep, cattle and goats in Australia. Experimental models of Johne’s disease in the natural host are logistically challenging due to the need for long term monitoring, as the disease can take several years to manifest. The pathogen utilises several mechanisms to establish infection within macrophages of the Peyer’s patches of the small intestine, leading to a wasting disease and eventual death in a proportion of infected individuals. MAP is known to interfere with the protective mechanisms employed by macrophages, however macrophage polarization in response to MAP exposure and its possible implications have not been studied. An experimental infection trial in cattle was conducted involving 20 exposed and 10 control animals, with disease progression monitored extensively over a period of nearly 5 years. We examined monocyte/macrophage polarization and responsiveness to antigens from MAP-exposed and unexposed animals and identified that at three years post-exposure, there was a heterogeneous macrophage activation pattern characterized by both classical (M1) and alternate (M2) phenotypes. Exposure of macrophages to antigens from MAP led to variation in the production of nitric oxide, interleukin-10 and tumour necrosis factor α. In order to understand this phenomenon, in vitro studies were conducted to examine the effects of cytokines and MAP exposure on macrophage polarisation status. Additionally, local macrophage populations derived directly from the infected gut lesions and associated lymph nodes were examined to determine if macrophage polarization is present locally. The results indicate that there are changes in the activation state and responsiveness of circulating monocytes/macrophages from MAP-exposed cattle and aid in further understanding local and systemic monocyte/macrophage changes in response to MAP infection.