Effect of Mycobacterial Infection in the Lupus-Prone MRL/lpr Mice: Enhancement of Life Span of Autoimmune Mice, Amelioration of Kidney Disease and Transient Decrease in Host Resistance

Abstract

We have used the MRL/lpr murine model of spontaneous lupus to investigate three questions in infection immunity: (1) does mycobacterial infection have any effect on the mortality of the autoimmunity-prone lpr mice?; (2) does the infection modify the progression of kidney disease of lpr lupus?; and (3) does the lpr gene change the resistance of mice to mycobacteria? Experimental infections were induced by intraperitoneal inoculation of 10⁷ viable bacilli of Mycobacterium avium in 3 months old MRL/lpr mice and also in congeneic MRL/+ mice (lacking the lpr gene). MRL mice were sacrificed 1, 2.5 and 4 months after the M. avium injection. We found that infection caused lowering of urine protein concentration in lpr mice as compared with age-matched lpr controls. Mycobacteriosis also induced a marked decrease in the mortality of lpr animals, e.g. 85% of infected lpr mice reached the age of 7 months whereas only 10% of control lpr mice reached the same age. MKL/lpr mice showed, after 1 and 2.5 months of infection, higher mycobacterial loads than the congeneic non-lpr MRL mice; after 4 months of infection, however, differences in M. avium loads between the two groups of MRL mice became not statistically significant. We conclude that: (1) mycobacterial infection increases the life span of lpr mice; (2) the infection slows down the progression of kidney disease in the lupus-prone lpr animals; (3) the autoimmunity gene lpr is associated with a transient decrease in host resistance to mycobacteria.

Key Words:

• Autoimmunity
• Infection
• Systemic Lupus Erythematosus
• Mycobacterium avium
• Glomerulonephritis
• Intracellular Parasites