SUSCEPTIBILITY TO TOXOPLASMOSIS - CORRELATION BETWEEN MACROPHAGE FUNCTION, BRAIN CYST FORMATION AND MORTALITY IN RATS

Rats are resistant to Toxoplasma infection, and in contrast to mice do not form cysts in their tissues. Because rats treated with beta adren ergics, corticosteroids or (60)cobalt are more susceptible to toxoplas mosis, we conducted experiments to investigate if the impaired resista nce of drug-treated rats is related to macrophage function or inductio n of cystogenic capacity. Our experiments in 0.7 or 1.2 mg/kg-corticos teroid or 12 Gy-(60)cobalt-treated rats indicated that the decreased s urvival rate (P<0.001 to P<0.0001, compared to infected-untreated or i nfected-unirradiated animals) was associated with a decrease of both m acrophage toxo-plasmastatic activity and intracellular killing (P<0.05 each group), compared to infected-untreated or infected-unirradiated rats. However in 9 Gy-(60)cobalt-treated animals the decreased surviva l rate (P<0.001, compared with control rats) was accompanied only by a decrease of the toxoplasmastatic activity in comparison to macrophage s of the control animals. Moreover in these animals, the release of NO 2- by these macrophages was poorly detectable (P<0.05) or completely i nhibited (P<0.01) in comparison with infected-untreated or infected-un irradiated rats. In contrast, in all groups of rats treated with high doses of beta adrenergic, the decreased survival (P<0.001 to P<0.0001, compared with untreated rats) was accompanied by values of intracellu lar killing and intracellular proliferation of Toxoplasma parasites th at did not significantly (P=ns each group) differ from macrophages of infected-untreated rats. Furthermore in the high beta adrenergic treat ed groups only small amounts of NO2- were detectable (P<0.05) in compa rison with control animals. In addition, our data in rats treated with 0.7 or 1.2 mg/kg of corticosteroid or 12 Gy of (60)cobalt indicated t hat the increased mortality was correlated to the presence of a small number of cysts in their brains (P<0.05; P=ns; P<0.01 respectively) in comparison to infected-untreated or infected-unirradiated rats. These results suggest that the susceptibility of drug-immunosuppressed rats is not due exclusively to a deficient macrophage function, but is pro bably also linked to immune mechanisms involved in the process of cyst ogenesis.