Multiple organ dysfunction in congenital murine toxoplasmosis.
Infection of gravid Nya: NYLAR (NYLAR), C57BL/6J (C57), and BALB/c mice with Toxoplasma gondii, on gestation day 7, resulted in fetal resorptions, abortions, and stillbirths. Fetal wastage (estimated) was 35 and 40% in the NYLAR and C57 strains and 55% in the BALB/c strain. Postnatally, pups were cachectic and growth-retarded, with some developing hind limb weakness, petechial lesions on ears and tail, and a blood-tinged nasal exudate. Only 13 of 97 BALB/c pups, 14 of 41 C57 pups, and 46 of 153 NYLAR pups survived the first month of life. At necropsy, swollen, blotched livers, enlarged spleens, pallid kidneys and pulmonary hemorrhages were observed. Cysts of T. gondii were detected in every pup, via press-smears of brain. Histologic examination revealed mineralizing cavitations, ventricular deformations, and periventricular edema in the central nervous system; extensive liver pathology marked by hepatocellular necrosis and calcification, sinusoidal dilatation, and giant cell granulomas; congestion of the spleen with blurring of red and white compartments and cavitations in the white pulp; and tubule and glomerular necrosis and calcification in the kidney. The pulmonary hemorrhages and dermal petechial lesions may reflect a bleeding diathesis due to hepatic insufficiency. The pathogenesis of congenital toxoplasmosis, in the 3 strains of mice, appears due to microvascular dysfunction characterized by dysregulation of hemostasis, perfusion failure, and multiple organ dysfunction, rather than to parasite-mediated cytopathology. We suggest that hematogenous dissemination and endothelial invasion by the parasite induced a systemic inflammatory response syndrome (i.e; toxoplasmic sepsis) leading to the microvascular dysfunction.
Department of Infectious Diseases, Tokai University School of Medicine, Isehara, Kanagawa, Japan.
Walter
W
Stahl
Masaki
M
Sekiguchi
Yoshimasa
Y
Kaneda
D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight; D002490:Central Nervous System / Q000473:pathology / Q000503:physiopathology; D004198:Disease Susceptibility / Q000175:diagnosis; D005260:Female; D005313:Fetal Death / Q000175:diagnosis; D006651:Histocytochemistry; D007668:Kidney / Q000473:pathology / Q000503:physiopathology; D008099:Liver / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D009102:Multiple Organ Failure / Q000209:etiology / Q000473:pathology*; D009929:Organ Size; D011247:Pregnancy; D011256:Pregnancy Outcome; D013154:Spleen / Q000473:pathology / Q000503:physiopathology; D014124:Toxoplasmosis, Animal / Q000150:complications* / Q000151:congenital / Q000469:parasitology