Oral Presentation HOST IMMUNE RESPONSE TO PLAGUE: EXPERIMENTAL Y. PESTIS CHALLENGE OF THE GUNNISONS PRAIRIE DOG JOSEPH D.

BUSCH1, Kacy R. Cobble1, Nate Stone1, Michael VerSteeg1, Roger Van Andel2, Jennifer Cordova3, Jeff Corcoran3, Julia Ramoz-Rodriguez4, Susan Smith4, Tonie Rocke4, and David M. Wagner1
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Center for Microbial Genetics and Genomics, Northern Arizona University, Flagstaff, AZ, 86011 2 University of California Berkeley, Berkeley, CA, 95720 3 Arizona Game and Fish Department, Seligman, AZ, 86337 4 USGS National Wildlife Health Center, Madison, WI 53711 Joseph.Busch@nau.edu, David.Wagner@nau.edu Prairie dogs are considered highly susceptible to Yersinia pestis, the causative agent of plague. A colony of Gunnisons prairie dogs (Cynomys gunnisoni) in the Aubrey Valley of northern Arizona appears to have survived several regional epizootics of plague whereas all other nearby colonies have been susceptible. To examine potential immune responses accounting for their survival, we trapped 60 wild C. gunnisoni from Aubrey Valley and Espee ranch (n=30 from each site) for a controlled laboratory challenge using the highly virulent Y. pestis strain CO92. Since the LD50 of CO92 is unknown for prairie dogs, we used three infection doses: low (500 cfu), medium (5,000 cfu), and high (50,000 cfu). Pre- and post-challenge blood sera were collected to evaluate cytokine levels using RodentMAP v2.0 and F1 antibody titers. Spleen, liver, and lung were also harvested from every individual at the end of the experiment (up to 40 days postinfection). Despite the high mortality known from plague epizootics in the wild (~99%), only 24 of the 60 animals died. Surprisingly, no mortality differences were observed between prairie dogs from the Aubrey Valley and Espee (Chi-square=2.5, d.f.=1, p=0.113). In the 36 survivors, antibody titers to plague F1 antigen were positively correlated to initial infection dose (Spearmans rank r=0.71, d.f.=34, p=0.00001). However, 16 of the survivors (44%) from the low and medium doses did not produce a detectable response to the F1 antigen. This raises the possibility that other antibodies are important in defense against plague, or that earlier immune pathways (acute-phase response, induced innate response, and T-cell pathways) can play an important role in clearing lower levels of Y. pestis infection. These results highlight the need to assess each arm of the immune response during experimental plague infections, because multiple mechanisms may be responsible for resistance to Y. pestis.