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Published on: July 12, 2024
Immunological changes associated with the treatment of pneumonic tularaemia in marmosets
Rachel E Ireland1, Alejandro Nunez2, James D Blanchard3
1Human and Biological Advantages, Defence Science and technology Laboratory, Salisbury, Wiltshire, United Kingdom.
Introduction:
Francisella tularensis is the causative agent of tularemia, a severe infection that can be fatal if untreated. There is a need for improved therapeutic options to enhance the efficacy of existing antibiotic regimens for severe tularemia and to reduce the risk of disease relapse. Novel formulations of ciprofloxacin have demonstrated protection against inhalational tularemia in murine and marmoset models; however, a detailed immunological characterisation of treatment response is required.
Methods:
Blood samples were collected from marmosets infected with a lethal dose of inhalational tularemia and treated with either oral ciprofloxacin or inhaled ciprofloxacin (Apulmiq®). Immunological responses were assessed longitudinally and compared with immunological changes previously observed in recovering human cases of tularemia.
Results:
Infected marmosets exhibited increased neutrophil levels, which, together with reduced HLA-DR expression, indicated severe infection. Rising circulating interferon-gamma (IFN γ) levels were followed by classical activation of macrophages as an initial attempt to control bacterial dissemination. Progressive disease was characterised by a marked depletion of neutrophils, excessive IFN γ production, and elevated levels of overactivated macrophages. In animals that responded successfully to treatment, these immunological parameters returned to baseline levels. Recovery was subsequently associated with increased T cell populations, particularly gamma delta T (γδ T) cells, and limited antibody production, suggesting the development of long-term immunity comparable to that observed in humans.
Discussion:
The observed immunological changes in marmosets closely mirror those reported in human tularemia, supporting the relevance of this model for studying disease progression and recovery. The capacity to monitor these immune parameters demonstrates the utility of the marmoset model in assessing the efficacy of new and novel antibiotic treatments for tularemia.
