Impairment of Interferon Production in Mice Infected with Mycobacterium lepraemurium 1

Abstract

Human lepromatous leprosy is a chronic intracellular infection that extensively involves the reticuloendothelial system and is associated with a generalized depression of cell-mediated immunity (1, 2). The mechanism of immunodepression in human leprosy is unknown. Experimental infection of rodents by Mycobacterium lepraemurium (3), however, is also associated with moderate impairment of the delayed allergic response and, thus, provides a model for investigation of this phenomenon. Leprous rodents are depressed in their ability to develop adjuvant arthritis (4) and contact sensitivity and skin homografts are retained significantly longer than in control animals (5). Anergy in murine leprosy is secondary to the infection itself and appears to be related to the multiplication of M. lepraemurium in reticuloendothelial tissue of the spleen, bone marrow, and lymph nodes.

Recent investigations have provided support for the concept that interferon production may represent one feature of the altered reactivity of “immune” lymphocytes or macrophages on re-exposure to an immunizing agent (6-9). Since mononuclear cells within the reticuloendothelial system are considered to be a major source of interferon production, these studies were carried out to determine if parasitization of these cells with mycobacteria might be associated with deficiencies of interferon production in addition to abnormalities of cellular immunity.

Methods. Mice. CF₁ female mice were obtained from Carworth Farms, Inc. All animals were housed under conditions of controlled humidity and temperature and a standardized 12-hr lighting cycle with food and water ad libitum.

M. lepraemurium infection. M. lepraemurium (Hawaiian strain) was kindly supplied by Dr. Byron Tepper, Leonard Wood Memorial Laboratories, Johns Hopkins University, Baltimore, MD. Six- to 8-week-old animals, weighing approximately 30 g were injected intraperitoneally with 0.6 ml of an inoculum containing 1 × 10⁹ M. lepraemurium harvested from pelvic fat pads of previously infected mice.