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 adrenergics, corticosteroids or 60cobalt are more susceptible to toxoplasmosis, we conducted experiments to investigate if the impaired resistance of drug-treated rats is related to macrophage function or induction of cystogenic capacity. Our experiments in 0.7 or 1.2 mg/kg-corticosteroid or 12 Gy-60cobalt-treated rats indicated that the decreased survival rate (P < 0.001 to P < 0.0001, compared to infected-untreated or infected-unirradiated animals) was associated with a decrease of both macrophage toxoplasmastatic activity and intracellular killing (P < 0.05 each group), compared to infected-untreated or infected-unirradiated rats. However in 9 Gy-60cobalt-treated animals the decreased survival rate (P < 0.001, compared with control rats) was accompanied only by a decrease of the toxoplasmastatic activity in comparison to macrophages of the control animals. Moreover in these animals, the release of NO2- by these macrophages was poorly detectable (P < 0.05) or completely inhibited (P < 0.01) in comparison with infected-untreated or infected-unirradiated 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 intracellular killing and intracellular proliferation of Toxoplasma parasites that did not significantly (P = ns each group) differ from macrophages of infected-untreated rats. Furthermore in the high beta adrenergic treated groups only small amounts of NO2- were detectable (P < 0.05) in comparison with control animals. In addition, our data in rats treated with 0.7 or 1.2 mg/kg of corticosteroid or 12 Gy of 60cobalt indicated that 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 probably also linked to immune mechanisms involved in the process of cystogenesis.
Benedetto
N
N
Institute of Microbiology, Second University of Naples, Italy.
Folgore
A
A
Ferrara
C
C
Galdiero
M
M
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001623:Betamethasone / Q000494:pharmacology; D001927:Brain Diseases / Q000209:etiology*; D003560:Cysts / Q000209:etiology*; D004198:Disease Susceptibility; D005938:Glucocorticoids / Q000494:pharmacology; D007165:Immunosuppression Therapy; D017737:Macrophages, Peritoneal / Q000276:immunology*; D008297:Male; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D014124:Toxoplasmosis, Animal / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D014916:Whole-Body Irradiation
D000319:Adrenergic beta-Antagonists; D005938:Glucocorticoids; D001623:Betamethasone; D011433:Propranolol