Neutrophils are critical for host defense against primary infection with the facultative intracellular bacterium Francisella tularensis in mice and participate in defense against reinfection

Abstract

It is generally believed that immunity to experimental infection with the facultative intracellular bacterium FranciseUla tularensis is an example of T-cell-mediated immunity that is expressed by activated macrophages and mediated by Francisella-specific T cells. According to the results presented herein, neutrophils are also essential for defense against primary infection with this organism. It is shown that mice depleted of neutrophils by treatment with the granulocyte-specific monoclonal antibody RB6-8C5 are rendered defenseless against otherwise sublethal doses of F. tularensis LVS inoculated intravenously or intradermally. In neutrophildepleted mice, the organism grew progressively in the livers, spleens, and lungs to reach lethal numbers, whereas infection was resolved in normal mice. Although neutrophils were found to contribute to resistance to reinfection, their participation was less important. The results suggest that neutrophils are needed for defense against primary infection because they serve to restrict the growth of F. tularensis before it reaches numbers capable of overwhelming a developing specific immune response. The exact way that neutrophils achieve this is not clear at this time, although it is probable that they contribute in ways other than by ingesting and killing the bacterium.

Interleukin‐1 deficiency in combination with macrophage depletion increases susceptibility to Pseudomonas aeruginosa bacteremia

“…We found that neutropenia induced by treatment with an anti-neutrophil Ab led to a dramatic increase in lethal sensitivity during bacteremia caused by P. aeruginosa, and that neutropenic mice died from smaller amounts of P. aeruginosa than the Cl 2 -MDP-or cyclophosphamide-treated mice. These results demonstrate the key role of neutrophils in protecting against systemic infection with P. aeruginosa or other pathogens, including Legionella pneumophila (20), Listeria monocytogenes (23), Salmonella typhimurium (21), and Francisella tularensis (24). However, neutropenia did not induce differences between the IL-1-deficient and WT mice in susceptibility to P. aeruginosa bacteremia.…”

“…It has previously been shown that mice with cyclophosphamide-induced bone marrow suppression, which increases their susceptibility to infection, are neutropenic (20)(21)(22)(23)(24). Moreover, Koh et al have generated a gut-derived sepsis model by treating animals with an anti-neutrophil mAb rather than cyclophosphamide (25).…”

Transcriptional profiling ofFrancisella tularensisinfected peripheral blood mononuclear cells: a predictive tool for tularemia

“…Immune response and apoptosis were well represented (Table 2). Early recruitment of inflammatory cells and production of proinflammatory cytokines (IL18, IL12p40, IFNg) are crucial for innate host defense against systemic LVS infection (Leiby et al, 1992;Sjöstedt et al, 1994;Elkins et al, 2003). These proinflammatory cytokines with increased expression patterns were represented in cluster 1 ( Table 2).…”

Role of neutrophils in innate resistance to Entamoeba histolytica liver infection in mice

“…It is well known that the neutrophil plays an important role in host resistance against different infections (Ferrante et al 1988, Rogers & Unanue 1993, Appelberg et al 1994, Sjöstedt et al 1994. Contrarily, experimental studies in amoebiasis in the hamster have claimed that tissue damage is mediated by lysosomal enzymes released from disintegrated neutrophils and mononuclear cells that accumulate around the amoebae and are killed by this parasite (Tsutsumi et al 1984).…”