A study of innate immune kinetics reveals a role for a chloride transporter in a virulent Francisella tularensis type B strain

A better understanding of how Francisella tularensis type B strains behave in macrophages is required to further elucidate the attenuating mechanisms of the Live Vaccine Strain, which is not FDA approved. Here we evaluate innate immune kinetics in human and murine macrophages following infection with a virulent type B strain compared with its attenuated counterpart, LVS, and a clcA mutant. Our results suggest that the disruption of the chloride transporter ClcA is one contributor to LVS attenuation and may be a target for a live attenuated vaccine against tularemia. AbstractTularemia is a zoonotic disease of global proportions.Francisella tularensis subspeciestularensis (type A) andholarctica (type B) cause disease in healthy humans, with type A infections resulting in higher mortality. Repeated passage of a type B strain in the mid ‐20th century generated the Live Vaccine Strain (LVS). LVS remains unlicensed, does not protect against high inhalational doses of type A, and its exact mechanisms of attenuation are poorly understood. Recent data suggest that live attenuated vaccines derived from type B may cross‐protect agains t type A. However, there is a dearth of knowledge regarding virulent type B pathogenesis and its capacity to stimulate the host's innate immune response. We therefore sought to increase our understanding of virulent type B in vitro characteristics using strain OR96‐0246 as a model. Adding to our k nowledge of innate immune kinetics in macrophages fol...
Source: MicrobiologyOpen - Category: Microbiology Authors: Tags: ORIGINAL ARTICLE Source Type: research