Cryptococcus neoformans-pulsed eosinophils inoculated intraperitoneally migrate to the spleen and Mesenteric lymph nodes where stimulate cell proliferation and Th1 cytokine production
Garro, Ana Paula; Chiapello, Laura Silvina and Masih, Diana Teresa
Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI), CONICET, Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Medina Allende y Haya de la Torre, Ciudad Universitaria, 5000, Córdoba, Argentina. dmasih@fcq.unc.edu.ar
Eosinophils (Eo) have been shown to be components of the inflammatory response to Cryptococcus neoformans (Cn) infection in rat and mouse. We have observed the presence of a large number of Eo in the granulomas surrounding Cn yeasts during disseminated cryptococosis in rats. Moreover, we have demonstrated that rat Eo stimulate in vitro the expansion of Cn-specific CD4+ and CD8+ T cells with a Th1 profile. Therefore, the aim of the present work was to study the role of Eo in the immune response to Cn infections.
Cn-pulsed Eo labeled with CFSE were inoculated intraperitoneally (ip) into naive rats to assess their potential to migrate to lymphoid organs (LO). Results indicated that CFSE+ Eo migrate from the peritoneal cavity to the Mesenteric lymph nodes (MLN) and spleen within 3 days.
On the other hand, Cn-pulsed Eo were inoculated ip into naive and Cn-infected rats to determine whether Eo could stimulate cell proliferation in vivo. Spleen and MLN cells recovered after 5 days of the inoculation were cultured in the presence of anti-CD3 MAb and it was observed that LO cells from rats inoculated with Cn-pulsed Eo had increased proliferation, compared with LO cells from rats that had received unpulsed Eo (p<0.01). Moreover, experiments were performed to analyze cytokines and total immunoglobulin (TIg) production by LO cells recovered from those rats. Spleen and MLN cells were cultured in the presence of heat killed Cn (HKC). The production of IL-12, IFNg, TNFa and TIg by LO cells isolated from rats inoculated with Cn-pulsed Eo was significantly increased, compared with that in control rats (p<0.01). However, the production of IL-4, IL-13 and IL-10 by LO cells was significantly decreased (p<0.01).
It was therefore concluded that Cn-pulsed Eo are capable of migrating to LO after their inoculation. Finally there, they can stimulate spleen and MLN cells proliferation, the increase of TIg production and the development of an antigen-specific Th1 cytokine response.
