Reduced immune responsiveness and lymphoid depletion in mice infected with Ehrlichia risticii

Abstract

The histopathology of the thymus and spleen and the response of spleen cells to mitogenic stimuli were evaluated in Sprague-Dawley CF-1 mice infected with Ehrlichia risticii. Intraperitoneal injection of 104 or 106 E. risticii-infected U-937 cells into mice resulted in 100% morbidity and partial mortality. Thymic atrophy became significant between 1 and 2 weeks postinfection and remained for the duration of the study. The atrophy appeared associated with antecedent destruction and rarefaction of lymphocytes, resulting in the loss of corticomedullary demarcation. Splenomegaly was prominent; significantly increased weights were detected 7 days postinfection. Histopathologic examination revealed rarefaction of lymphocytes around central arteries, the presence of necrotic debris in histiocytes, and replacement of erythropoiesis by granulopoiesis in the red pulp. Marked and acute reduction of in vitro proliferative responses of spleen cells to concanavalin A (ConA) and phytohemagglutinin were observed in mice infected with 104 or 106 E. risticii-infected U-937 cells. Interleukin-2 activity in the supernatant of ConA-stimulated spleen cells was also severely reduced. Both changes were time-and dose-dependent and were not associated with decreased spleen cell viability. Neither morbidity nor mortality occurred in mice infected with 102 E. risticii-infected U-937 cells. Although there was temporal reduction in phytohemagglutinin-driven lymphocyte proliferation, reduction in neither ConA-driven lymphocyte proliferation nor interleukin-2 activity was observed with this dosage. All E. risticii-inoculated mice seroconverted between days 18 and 25, as detected by the indirect fluorescent-antibody procedure. The findings indicate for the first time the hypoimmune responsiveness and histopathologic changes in lymphoid organs associated with E. risticii infection.

Comparison of PCR and culture to the indirect fluorescent-antibody test for diagnosis of Potomac horse fever

“…The PCR was also useful in detecting subclinical infection with E. risticii Ohio 380 in mice. Mice have been used as experimental infection or disease models for PHF (16,20). Since it is very difficult to monitor subclinical infection in mice by culture isolation due to the small amount of blood that is available, PCR is useful for experimentation with the mouse model.…”

“…Experimentally inoculated mice. Mice inoculated with 10 4 E. risticii Ohio 380-infected P388D 1 cells did not develop any clinical signs, unlike mice inoculated with the same number of a 1984 Virginia isolate of E. risticii (20). The 16S rRNA gene of E. risticii was detected by nested PCR amplification of the blood of inoculated CF1 mice on days 1, 3, 7, 10, 13, and 17 p.i., indicating subclinical infection ( Fig.…”

“…(17). The E. risticii 16S rRNA gene PCR product was detected by agarose gel electrophoresis by a nested PCR amplification of DNA extracted from blood mononuclear cell fractions and feces of the pony on days 1,6,8,11,13,15,18,20,22,25,28, and 32 p.i. (Table 1; Fig.…”

Retention and attempted mechanical transmission of Ehrlichia risticii by Stomoxys calcitrans

“…Using our average blood ingestion values, we estimated that S.calcitrans ingested e3.2 X lo3 E.risticiiinfected mouse cells in the retention study and ingested =2.7 x 10' E.risticii-infected cells during the 20s feeding of the transmission study. Mice are susceptible to E.risticii infections (Jenkins et al, 1985;Johnson & Rikihisa, 1988), serve as a suitable model for study E.risticii in the laboratory (Rikihisa et a/., 1987;Kaylor et a/., 1991;Williams, 1992), and have seroconverted when injected with 1 X lo2 E. risticii-infected mouse macrophage cells (Rikihisa et ul., 1987). Butler et al (1977) reported that S.caZcitrans can regurgitate whole blood cells, as well as serum, from previous meals.…”

Antibody response to Ehrlichia risticii and antibody reactivity to the component antigens in horses with induced Potomac horse fever

“…A similar transient reduction in the cell-mediated immune response, as measured by in vitro lymphocyte blastogenesis and interferon production, has been observed in these horses at about 3 weeks PI (unpublished data). Recently, Rikihisa et al (7) reported reduced immune responsiveness and lymphoid depletion in mice infected with E. risticii. Thus, it seems that during the course of E. risticii infection there may be a transient degeneration or destruction of lymphoid cells, causing a decreased immune responsiveness which may be one of the mechanisms of pathogenesis in this disease.…”