The protective role of macrophages in Francisella tularensis infection (MPF3P.819)

Abstract

Francisella tularensis causes lethal pneumonia following infection of the lungs. F. tularensis is considered to be an intracellular pathogen that targets macrophages for replication. We therefore hypothesized that depletion of alveolar macrophages would impede bacterial replication and improve host survival. However, it was found that macrophages are essential for survival of F. tularensis infection and depletion of these cells reduced survival rates following infection. Mice with a macrophage-specific defect in interferon gamma (IFN-γ) signaling (MIIG mice) were also highly sensitive to infection, exhibiting reduced survival rates, reduced mean time to death, and increased bacterial burdens in lungs, liver, and spleen relative to wild-type mice. We have previously found that treatment with exogenous interleukin 12 (IL-12) protects against F. tularensis infection; this protection was lost in MIIG mice. MIIG mice also exhibited reduced neutrophil recruitment to the lungs following infection. Systemic neutrophil depletion was found to render mice highly sensitive to pneumonic F. tularensis infection. Furthermore, IL-12-mediated protection required NADPH activity. These results indicate that lung macrophages serve a critical protective role in pneumonic F. tularensis infection. Macrophages require IFN-γ signaling to mediate protection, which ultimately results in recruitment of neutrophils to further aid in survival from infection.

Francisella tularensis: a zoonotic pathogen among wild rodents and arthropods - a possible threat in future

“…Lung infection was mostly associated with farming activities (Seiwald et al, 2020). The periprosthetic joint infections have been reported in many occasions (Steiner et al, 2014;Chrdle et al, 2019).…”

“…In addition, ability to LPS alteration and presence of pili in the cells are considered as protection mechanism against host immune mechanism (Rowe and Huntley, 2015). Pathogenicity consists of 17 open reading frames which is believed to be essential for the pathogenesis (Steiner et al, 2014). The reactive oxygen species (ROS) and nitrogen species is also an essential component of Francisella virulence mechanism, enzyme KatG deactivates these two-protective mechanisms of the host cell (Steiner et al, 2014).…”

“…Pathogenicity consists of 17 open reading frames which is believed to be essential for the pathogenesis (Steiner et al, 2014). The reactive oxygen species (ROS) and nitrogen species is also an essential component of Francisella virulence mechanism, enzyme KatG deactivates these two-protective mechanisms of the host cell (Steiner et al, 2014). SodB and SodC which encoded for superoxide dismutase are also required for the resistance against superoxide radicals (Steiner et al, 2014).…”

“…The reactive oxygen species (ROS) and nitrogen species is also an essential component of Francisella virulence mechanism, enzyme KatG deactivates these two-protective mechanisms of the host cell (Steiner et al, 2014). SodB and SodC which encoded for superoxide dismutase are also required for the resistance against superoxide radicals (Steiner et al, 2014). Francisella enter into the macrophages with a specific mechanism called "looing phagocytosis" which consists of a large volume of space around the bacterium, surface receptors playing a vital role in phagocytosis such as mannose receptors, Fc receptors and complement receptors (Steiner et al, 2014).…”

“…SodB and SodC which encoded for superoxide dismutase are also required for the resistance against superoxide radicals (Steiner et al, 2014). Francisella enter into the macrophages with a specific mechanism called "looing phagocytosis" which consists of a large volume of space around the bacterium, surface receptors playing a vital role in phagocytosis such as mannose receptors, Fc receptors and complement receptors (Steiner et al, 2014). In addition, Iron is also an essential element for survival of Francicella in a host cell (Steiner et al, 2014).…”