Analysis of cerebrospinal fluid in healthy rabbits and rabbits with clinically suspected encephalitozoonosis.

Samples of uncontaminated cerebrospinal fluid (csf) were collected from the cisterna magna of 20 healthy laboratory rabbits and 21 pet rabbits with vestibular disease and/or paresis due to clinically suspected encephalitozoonosis. In the healthy rabbits' csf the leucocyte count was

Efficacy of gamma interferon and specific antibody for treatment of microsporidiosis caused by Encephalitozoon cuniculi in SCID mice.

Microsporidia are eukaryotic, obligate, intracellular protists that are emerging pathogens in immunocompromised hosts, including AIDS patients and organ transplant recipients. The efficacy of gamma interferon (IFN-gamma) for the treatment of microsporidiosis caused by Encephalitozoon cuniculi was studied by means of adoptive transfer and IFN-gamma administration in SCID mice. While the adoptive transfer of CD4(+) T cells from immunocompetent mice prolonged survival of SCID mice infected perorally with E. cuniculi, survival was not improved by adoptive transfer of CD4(+) T lymphocytes from IFN-gamma-deficient mice. The protective effect of IFN-gamma was confirmed in cytokine therapy experiments in which SCID mice receiving IFN-gamma survived significantly longer than mice receiving mock injections. The administration of serum containing specific antibodies against E. cuniculi was found to prolong the survival of concurrently IFN-gamma-treated SCID mice. The data presented in this study suggest that IFN-gamma is potentially useful as a cytokine therapy for microsporidiosis, especially in CD4(+) T-cell-deficient patients.

Induction of a rapid and strong antigen-specific intraepithelial lymphocyte response during oral Encephalitozoon cuniculi infection.

Encephalitozoon cuniculi continues to pose a problem for immunocompromised patients. Previous studies from our laboratory have elucidated the importance of the CD8(+) T cell subset in the protection against systemic parasite infection. There have been no studies related to the mucosal immunity induced against this orally acquired pathogen. In the present study, the immune response generated in the gut after oral E. cuniculi infection was evaluated. An early and rapid increase of the intraepithelial lymphocyte (IEL) population of orally infected animals was observed. This increase in the IEL population started as early as day 3 and peaked at day 7 postinfection with persistent elevation thereafter. At day 7 postinfection, IELs expressed strong cytokine messages (IFN-gamma and IL-10) and were highly cytotoxic for parasite-infected syngeneic macrophages. At an E:T ratio of 80:1, these cells were able to cause >60% Ag-specific target cell lysis. A significant increase in the CD8alphaalpha subset of IEL in response to an oral E. cuniculi infection was observed. To the best of our knowledge, such an early expansion of an IEL population exhibiting strong ex vivo cytotoxicity has not been reported with infectious models. These data suggest that IELs act as important barriers for multiplication of this organism leading to the successful resolution of infection. The protective role of IELs may be due both to their inflammatory (IFN-gamma production and cytotoxic response) as well as immunoregulatory (IL-10 production) properties.

Overt fatal and chronic subclinical Encephalitozoon cuniculi microsporidiosis in a colony of captive emperor tamarins (Saguinus imperator).

The course of an infection with the microsporidian Encephalitozoon cuniculi in a colony of captive emperor tamarins (Saguinus imperator) is described. In two litters, the infection was associated with overt disease and death of all infants. Immunohistochemistry for E. cuniculi showed generalized infections, and histopathologic evaluation revealed systemic vasculitis and disseminated mixed inflammatory cell infiltration with and without necrosis in several organs. Serologically, some of the juvenile animals presented with high titres for Encephalitozoon, while the adults had low titres. The E. cuniculi "dog strain" was identified by molecular means for the first time in Europe. The origin of the infection appeared to be a pair of breeding adults that originated from the US. Our data suggest that the organism persisted over years in the colony, and that subclinically infected animals most likely were involved in perpetuating the infection. Efforts should be made to ascertain if this microorganism is present in other captive populations of this endangered monkey species and to prevent its further spreading.

Immune response to Encephalitozoon cuniculi infection.

Microsporidia are obligate intracellular parasites, which can cause complications in immunocompromised individuals. Very little is known about the host immune response generated against these infectious agents. Encephalitozoon cuniculi is the best studied microsporidian and the protective immune response against this parasite is mediated by cytotoxic CD8(+) T cells.

CD8+ CTLs are essential for protective immunity against Encephalitozoon cuniculi infection.

Encephalitozoon cuniculi is a protozoan parasite that has been implicated recently as a cause of opportunistic infection in immunocompromised individuals. Protective immunity in the normal host is T cell-dependent. In the present study, the role of individual T cell subtypes in immunity against this parasite has been studied using gene knockout mice. Whereas CD4-/- animals resolved the infection, mice lacking CD8+ T cells or perforin gene succumbed to parasite challenge. The data obtained in these studies suggest that E. cuniculi infection induces a strong and early CD8+ T response that is important for host protection. The CD8+ T cell-mediated protection depends upon the CTL activity of this cell subset, as the host is rendered susceptible to infection in the absence of this function. This is the first report in which a strong dependence upon the cytolytic activity of host CD8+ T cells has been shown to be important in a parasite infection.