The Innate Immune Response in the Marmoset during the Acute Pneumonic Disease Caused by Burkholderia pseudomallei

Burkholderia pseudomallei is the causative agent of melioidosis, a severe human infection that is difficult to treat with antibiotics and for which there is no effective vaccine. Development of novel treatments rely upon appropriately characterized animal models. The common marmoset (Callithrix jacchus) has been established at Defense Science and Technology laboratories (DSTL) as a model of melioidosis. Further analysis was performed on samples generated in these studies to provide a description of the innate immune response. Many of the immunological features described, (migration/activation of neutrophils and macrophages, activation of T cells, elevation of key cytokines IFNγ, TNF-α, IL-6, and IL-1β) have been observed in acute melioidosis human cases and correlated with prognosis. Expression of the MHCII marker (HLA-DR) on neutrophils showed potential as a diagnostic with 80% accuracy when comparing pre- and postchallenge levels in paired blood samples. Discriminant analysis of cell surface, activation markers on neutrophils combined with levels of key cytokines, differentiated between disease states from single blood samples with 78% accuracy. These key markers have utility as a prototype postexposure, presymptomatic diagnostic. Ultimately, these data further validate the use of the marmoset as a suitable model for determining efficacy of medical countermeasures against B. pseudomallei.