Characterization of Immune Responses in Tuberculosis Positive Asian Elephants (Elephas maximus)
American Association of Zoo Veterinarians Conference 2013

Jennifer Landolfi1*, DVM, DACVP; Michele Miller2, DVM, MPH, PhD; Karen Terio1, DVM, PhD, DACVP

1Zoological Pathology Program, University of Illinois, Maywood, IL, USA; 2Rare Species Conservatory Foundation, Loxahatchee, FL, USA


Tuberculosis is an important health concern for Asian elephant (Elephas maximus) populations worldwide. Most infections are due to Mycobacterium tuberculosis, though mechanisms underlying tuberculosis susceptibility are unknown.3,4 In humans and other species, tuberculosis susceptibility is dependent on the host immune response following infection. Disturbances in the balance between host cell-mediated and humoral immune responses are central to disease pathogenesis.5,7 Recent studies have begun to describe contributions of elephant immune responses to tuberculosis. Real time RT-PCR measurement of cell-mediated (TH1) and humoral (TH2) cytokine levels in baseline peripheral blood samples from tuberculosis positive and negative elephants showed trends towards higher expression of some TH1 cytokines in positive elephants, though findings were not significant.1,2 Subsequent related studies were conducted to examine functional responses of peripheral blood mononuclear cells from 8 tuberculosis positive and 8 negative elephants following mycobacterial antigen stimulation. Results showed that samples from positive elephants exhibited enhanced proliferation and greater production of TH1 cytokines, including tumor necrosis factor-a, interluekin-12, and interferon-g, than tuberculosis negative elephants. Additionally, examination of elephant pulmonary tuberculosis lesions (n=14; 9 affected 5 controls) using light microscopy, immunohistochemistry, and in situ hybridization illustrated distinct patterns of inflammation with morphology and local cytokine expression reminiscent of both human latent and active tuberculosis lesions.6 Altogether, results of these investigations have indicated the elephant immune system does play a role in tuberculosis pathogenesis. Ideally, the foundation of knowledge established by these findings will serve to promote continued investigation of elephant tuberculosis immunopathogenesis for the long-term conservation of this endangered species.

Literature Cited

1.  Landolfi, J.A., S.K. Mikota, J. Chosy, K.P. Lyashchenko, K. Giri, K. Gairhe, and K.A. Terio. 2010. Characterization of systemic immune responses in Asian elephants (Elephas maximus) seropositive for Mycobacterium spp. J. Zoo Wildl. Med. 41(3): 445–455.

2.  Landolfi, J.A., S.A. Schultz, S.K. Mikota, and K.A. Terio. 2009. Development and validation of cytokine quantitative, real time RT-PCR assays for characterization of Asian elephant immune responses. Vet. Immunol. Immunopath. 131: 73–78.

3.  Mikota, S.K., and J.N. Maslow. 2011. Tuberculosis at the human-animal interface: an emerging disease of elephants. Tuberculosis. 91(3): 208–211.

4.  Mikota, S.K., L. Peddie, J. Peddie, R. Isaza, F. Dunker, G. West, W. Lindsay, R.S. Larsen, M.D. Salman, D. Chatterjee, J. Payeur, D. Whipple, C. Thoen, D.S. Davis, C. Sedgwick, R.J. Montali, M. Ziccardi, and J. Maslow. 2001. Epidemiology and diagnosis of Mycobacterium tuberculosis in captive Asian elephants (Elephas maximus). J. Zoo Wildl. Med. 32(1): 1–16.

5.  Raja, A. 2003. Immunology of tuberculosis. Indian J. Med. Res. 120(4): 213–232.

6.  Ulrichs, T., G.A. Kosmiadi, S. Jorg, L. Pradl, M. Titukhina, V. Mishenko, N. Gushina, and S.H.E. Kaufmann. 2005. Differential organization of the local immune response in patients with active cavitary tuberculosis or with nonprogressive tuberculoma. J. Infect. Dis. 192: 89–97.

7.  Zuñiga, J., D. Torres-García, T. Santos-Mendoza, T.S. Rodriguez-Reyna, J. Granados, and E.J. Yunis. 2012. Cellular and humoral mechanisms involved in the control of tuberculosis. Clin. Dev. Immunol. 2012:193923. doi: 10.1155/2012/193923. Epub 2012 May 17.


Speaker Information
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Jennifer Landolfi, DVM, DACVP
Zoological Pathology Program
University of Illinois
Maywood, IL, USA

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