Characterization of lethal inhalational infection with Francisella tularensis in the common marmoset (Callithrix jacchus)

Abstract

The intracellular Gram-negative pathogen Francisella tularensis is the causative agent of tularaemia and is prevalent in many countries in the northern hemisphere. To determine whether the common marmoset (Callithrix jacchus) would be a suitable non-human primate model of inhalational tularaemia, a pathophysiology study was undertaken. Ten animals were challenged with approximately 10(2) c.f.u. F. tularensis strain SCHU S4 (F. tularensis subsp. tularensis). To look for trends in the infection, pairs of animals were sacrificed at 24 h intervals between 0 and 96 h post-challenge and blood and organs were assessed for bacteriology, pathology and haematological and immunological parameters. The first indication of infection was a raised core temperature at 3 days post-challenge. This coincided with a number of other factors: a rapid increase in the number of bacteria isolated from all organs, more pronounced gross pathology and histopathology, and an increase in the immunological response. As the disease progressed, higher bacterial and cytokine levels were detected. More extensive pathology was observed, with multifocal lesions seen in the lungs, liver and spleen. Disease progression in the common marmoset appears to be consistent with human clinical and pathological features of tularaemia, indicating that this may be a suitable animal model for the investigation of novel medical interventions such as vaccines or therapeutics.

Fig. 1.

Bacterial load isolated from selected marmoset organs at different times post-challenge with ∼10² c.f.u. inhalational F. tularensis [n=2 for all time points, except terminal animals where n=6 (samples obtained from a previous study; Nelson et al., 2009)].

Fig. 2.

Cellular populations isolated from selected marmoset organs at different times after challenge with ∼10² c.f.u. inhalational F. tularensis [n=2 for all time points, except naïve control animals (baseline values) where n=3]. (a) Lymphocyte populations in the lung. (b) T-cell summary.

Fig. 3.

Haematoxylin and eosin-stained sections from marmosets infected with ∼10² c.f.u. F. tularensis by the airborne route. (a) Lung section from a marmoset at 72 h after challenge by the airborne route showing focal pneumonia. (b) Lung section from a marmoset at 96 h post-challenge showing extensive bronchopneumonia. (c) Liver section from a marmoset at 96 h post-challenge showing necrotizing hepatitis with the formation of microabscesses. (d) Spleen section from a marmoset at 96 h post-challenge showing necrotizing splenitis with the formation of microabscesses. Magnification: ×100 (a–c); ×200 (d).