Delayed presence of alternatively activated macrophages during a Francisella tularensis infection

• Francisella tularensis infection caused severe pathology in a BALB/c intranasal model.
• Using immunohistochemistry relative proportions of classically and alternatively activated macrophages were determined.
• The presence of classically activated macrophages coincides with the appearance of pathology.
• Alternatively activate macrophages are only detected shortly before death and in low numbers.

Francisella tularensis is an intracellular bacterium that has the ability to multiply within the macrophage. The phenotype of a macrophage can determine whether the infection is cleared or the host succumbs to disease. Previously published data has suggested that F. tularensis LVS actively induces the alternative phenotype as a survival mechanism. In these studies we demonstrate that this is not the case for the more virulent strain of F. tularensis SCHU-S4. During an intranasal mouse model of infection, immuno-histochemistry identified that iNOS positive (“classical”) macrophages are present at 72 h post-infection and remain high (supported by CCL-5 release) in numbers. In contrast, arginase/FIZZ-1 positive (“alternative”) cells appear later and in low numbers during the development of the disease tularemia.