NEUTROPHILS ARE CRITICAL FOR HOST-DEFENSE AGAINST PRIMARY INFECTION WITH THE FACULTATIVE INTRACELLULAR BACTERIUM FRANCISELLA-TULARENSIS IN MICE AND PARTICIPATE IN DEFENSE AGAINST REINFECTION

It is generally believed that immunity to experimental infection with the facultative intracellular bacterium Francisella tularensis is an e xample of T-cell-mediated immunity that is expressed by activated macr ophages 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 de pleted of neutrophils by treatment with the granulocyte-specific monoc lonal antibody RB6-8C5 are rendered defenseless against otherwise subl ethal doses of F. tularensis LVS inoculated intravenously or intraderm ally. In neutrophil-depleted mice, the organism grew progressively in the livers, spleens, and lungs to reach lethal numbers, whereas infect ion was resolved in normal mice. Although neutrophils were found to co ntribute to resistance to reinfection, their participation was less im portant. The results suggest that neutrophils are needed for defense a gainst primary infection because they serve to restrict the growth of F. tularensis before it reaches numbers capable of overwhelming a deve loping specific immune response. The exact way that neutrophils achiev e this is not clear at this time, although it is probable that they co ntribute in ways other than by ingesting and killing the bacterium.