SUSCEPTIBILITY OF BEIGE MICE TO MYCOBACTERIUM-AVIUM - ROLE OF NEUTROPHILS

The beige mutation in C57BL/6 mice has been shown to increase the susc eptibility to infection by Mycobacterium avium. In this study, we conf irmed those results and showed that the effect of the beige mutation w as most obvious after infection with a strain of lower virulence than with a highly virulent isolate of M. avium. The dissemination of M, av ium from the gut was observed with both C57BL/6 and beige mice but was faster in the latter. The expression of gamma interferon (IFN-gamma) and the priming for tumor necrosis factor production during an in vivo infection were similar between beige and immunocompetent C57BL/6 mice . IFN-gamma produced during the infection of beige mice was protective in the spleen, and the administration of recombinant IFN-gamma restor ed the resistance in the spleen to levels similar to those found in co ntrol mice. There were no histological differences between wild-type a nd beige mice with respect to granuloma formation in the liver. The in creased susceptibility of beige mice to M. avium as manifested in the liver was reduced by transfusing neutrophils from wild-type C57BL/6 mi ce. Likewise, depletion of neutrophils from C57BL/6 mice rendered them as susceptible to in. avium infection of the liver as beige mice. Our results point to the participation of neutrophils in the defect of be ige mice in addition to other defects. Furthermore, these results show that neutrophils play a significant role in the defense mechanisms ag ainst mycobacterial infections and that beige animals may be a useful model for study of the role of neutrophils in mycobacteriosis.