Abstract
Background Francisella tularensis is an intercellular bacterium often causing fatal disease when inhaled. Previous reports have underlined the role of cell-mediated immunity and IFNγ in the host response to Francisella tularensis infection.Methodology/Principal FindingsHere we provide evidence for the involvement of IL-17A in host defense to inhalational tularemia, using a mouse model of intranasal infection with the Live Vaccine Strain (LVS). We demonstrate the kinetics of IL-17A production in lavage fluids of infected lungs and identify the IL-17A-producing lymphocytes as pulmonary γδ and Th17 cells. The peak of IL-17A production appears early during sub-lethal infection, it precedes the peak of immune activation and the nadir of the disease, and then subsides subsequently. Exogenous airway administration of IL-17A or of IL-23 had a limited yet consistent effect of delaying the onset of death from a lethal dose of LVS, implying that IL-17A may be involved in restraining the infection. The protective role for IL-17A was directly demonstrated by in vivo neutralization of IL-17A. Administration of anti IL-17A antibodies concomitantly to a sub-lethal airway infection with 0.1×LD50 resulted in a fatal disease.ConclusionIn summary, these data characterize the involvement and underline the protective key role of the IL-17A axis in the lungs from inhalational tularemia.
Highlights
Francisella tularensis (Ft), the causative agent of tularemia, is a small gram-negative facultative intracellular bacterium, which can infect a broad spectrum of hosts
C57BL/6 mice were infected with 105 CFU of Live Vaccine Strain (LVS), the equivalent of 1006LD50, which results in the death of all mice by day 5–6 post infection (Figure 1A)
Live bacteria can be detected in the mediastinal lymph node (MdLN) already by 4 h, with a dramatic 1000-fold increase during the first two days [9]
Summary
Francisella tularensis (Ft), the causative agent of tularemia, is a small gram-negative facultative intracellular bacterium, which can infect a broad spectrum of hosts. The infectious dose required to cause human infection varies with the Francisella strain and route of entry [3]. Ft subspecies tularensis (type A subspecies) is a highly infectious and virulent pathogen that can cause a fulminant and often fatal disease by inhalational exposure to as few as 10 microorganisms. Previous reports have shown that inhaled LVS infects preferentially airway macrophages and dendritic cells, as early as 1 h after infection, and continues to replicate within them [7,8]. Francisella tularensis is an intercellular bacterium often causing fatal disease when inhaled. Previous reports have underlined the role of cell-mediated immunity and IFNc in the host response to Francisella tularensis infection
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