Citation:

Miller, T A. AND F W. Schaefer III. CHANGES IN MOUSE CIRULATING LEUKOCYTE NUMBERS IN C57BL/6 MICE IMMUNOSUPPRESSED FOR CRYPTOSPORIDIUM PARVUM OOCYST PRODUCTION. Veterinary Parasitology. Elsevier, Shannon, Ireland, 143:99-105, (2007).

Impact/Purpose:

(1) Conduct laboratory evaluations of new methods for detection of protozoan parasites. (2) Determine the infective dose of parasitic protozoa to hosts given a variety of models that will assist in estimating the public health significance at various levels of occurrence. The work in this task will support CCL2 and 3 and will be completed by 9/05.

Description:

The Iowa strain of Cryptosporidium parvum will not propagate in immunocompetent mice, but will successfully infect genetically immunocompromised Nude or SCID mice as well as immunocompetent mice which have been immunosuppressed with glucocorticoids. Using dexamethasone - tetracycline is one method for immunosuppressing mice for the production of C. parvum oocysts. However, dexamethasone induced immunosuppression is variable, because it is dependent on the total daily water consumption of each individual mouse. In an attempt to more accurately characterize the immunocompromised state for future studies on the infectivity of Cryptosporidium in immunocompromised mice, the changes in circulating leukocytes and other immune system associated organs before, during and after dexamethasone suppression were analyzed. The dexamethasone induced immunocompromised state was associated with greater than 90 percent sustained drop in the circulating T-lymphocyte count, a greater than 700 percent increase in circulating mature segmented neutrophils and a severe depletion of circulating monocytes. The thymus and spleen decreased in size by over 80 percent. Oocyst shedding in suppressed mice started within four days of oocyst inoculation and persisted for six days after dexamethasone withdrawal. Circulating neutrophils rose dramatically by 714 percent while on dexamethasone; seven days after dexamethasone withdrawal circulating neutrophils still were 549 percent higher than normal. Circulating CD3 and CD4 lymphocytes remained 85 to 90 percent below normal while on dexamethasone and for seven days after discontinuing dexamethasone. CD8 lymphocyte numbers initially decreased by 90 percent, but rose even while on dexamethasone and even with severe thymic involution. At day seven post dexamethasone treatment, the spleen was 119 mm3, approximating normal. After fourteen days of dexamethasone withdrawal, the CD8 counts were only 1.6 percent below normal while the CD3 and CD4 counts were still 66 percent below normal. The thymus now was about three quarters of its normal size. The rise in circulating CD8 lymphocytes when oocyst production stopped suggests that CD8 positive lymphocytes may play a significant role in vivo in clearing the parasite.

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