ACQUISITION OF AUTOIMMUNITY GENES BY NEW-ZEALAND MICE IS ASSOCIATED WITH NATURAL-RESISTANCE TO INFECTION BY MYCOBACTERIA

New Zealand (NZ) mouse strains comprise both autoimmune and non-autoimmune animals: NZ black (NZB) mice and the F1 hybrid ( NZB W) of NZB and NZ white (NZW) mice show spontaneous autoimmune disease by 6 months of age and die before the first year of age from renal disease, while NZW mice do not show autoimmune disorders. We investigated whether the autoimmunity-prone NZ animals (NZB and NZB W) differ from the non-autoimmune NZW mice in susceptibility/resistance to mycobacterial infection. The three groups of NZ mice were infected by intraperitoneal inoculation of 108 colony forming units (cfu) of Mycobacterium avium. The M. avium infection was induced in 3-month-old mice (i.e., before NZB and NZB W mice develop autoimmune disease) and studied for 4 months. Infected NZB and NZB W mice showed evidence of renal disease at 2 and 4 months of infection (but not at 1 month). The non-autoimmune NZW mice were found to be susceptible to M. avium since they allowed massive proliferation (4-5 log growth) of the bacilli in liver and spleen. In contrast, both groups of autoimmunity-prone mice (NZB and NZB W) were resistant to M. avium since their mycobacterial loads remained below the value of the initial inoculum. We conclude that in NZ mice the acquisition of autoimmunity genes is associated with expression of natural resistance to mycobacterial infection. This is consistent with the view that autoimmunity genes may have been evolutionarily selected because of their association with increased resistance of the host to infections by intracellular parasites. © 1992.