Eosinophils Regulate Type 2 Immune Responses Following Infection with the Nematode Trichinella spiralis

Eosinophils are multifunctional leukocytes implicated in protection against helminth infections. Although eosinophils comprise between 1~5% of peripheral blood leukocytes, they primarily reside in the gastrointestinal tract under homeostatic conditions, and rapidly proliferate upon parasitic infection. Intestinal infection with Trichinella spiralis (T. spiralis) induces eosinophilia when the parasite enters the larval stages and larvae finally migrate to the skeletal muscle. Eosinophils are known to mediate parasite death through antibody-dependent cellular cytotoxicity. In this study, we aimed to address the functional significance of eosinophils in the intestinal phase of T. spiralis infection by analysis of immune responses in the Peyer's patch (PP) of infected BALB/c and eosinophil-ablated ΔdblGATA mice. Trafficking of eosinophils to the PP was significantly increased, with upregulation of interleukin-5 at 14 days post infection. Eosinophil deficiency led to a significant augmentation of serum immunoglobulin (Ig) M and IgG1 antibody levels. In accordance with this, IgG1+ B cells in the PP were substantially increased in ΔdblGATA mice compared to that in BALB/c mice. Transforming growth factor-β expression in the PP of infected ΔdblGATA mice was significantly decreased compared to that in BALB/c mice, whereas the number of T. spiralis larvae in the diaphragm was increased. Taken together, these findings indicate that eosinophils contribute to the regulation of Th2 immune responses, and protect the host from T. spiralis attempting to establish larvae in the skeletal muscle.

Toll-Like Receptor Gene Expression during Trichinella spiralis Infection

In Trichinella spiralis infection, type 2 helper T (Th2) cell-related and regulatory T (T(reg)) cell-related immune responses are the most important immune events. In order to clarify which Toll-like receptors (TLRs) are closely associated with these responses, we analyzed the expression of mouse TLR genes in the small intestine and muscle tissue during T. spiralis infection. In addition, the expression of several chemokine- and cytokine-encoding genes, which are related to Th2 and T(reg) cell mediated immune responses, were analyzed in mouse embryonic fibroblasts (MEFs) isolated from myeloid differentiation factor 88 (MyD88)/TIR-associated proteins (TIRAP) and Toll receptor-associated activator of interferons (TRIF) adapter protein deficient and wild type (WT) mice. The results showed significantly increased TLR4 and TLR9 gene expression in the small intestine after 2 weeks of T. spiralis infection. In the muscle, TLR1, TLR2, TLR5, and TLR9 gene expression significantly increased after 4 weeks of infection. Only the expression of the TLR4 and TLR9 genes was significantly elevated in WT MEF cells after treatment with excretory-secretory (ES) proteins. Gene expression for Th2 chemokine genes were highly enhanced by ES proteins in WT MEF cells, while this elevation was slightly reduced in MyD88/TIRAP-/- MEF cells, and quite substantially decreased in TRIF-/- MEF cells. In contrast, IL-10 and TGF-beta expression levels were not elevated in MyD88/TIRAP-/- MEF cells. In conclusion, we suggest that TLR4 and TLR9 might be closely linked to Th2 cell and T(reg) cell mediated immune responses, although additional data are needed to convincingly prove this observation.

Utilidad del albendazol/quinfamida en el tratamiento de la fase intestinal de la infección por Trichinella spiralis en modelo murio / Utility of abendazole/quinfamide in the treatment ofintestinal phase of infection in murine model Trichinella spiralis

La triquinelosis es una enfermedad parasitaria ocasionada por el nematodo Trichinella spiralis. Actualmente el tratamiento utilizado para la triquinelosis es la administración de albendazol o mebendazol. Estos medicamentos son efectivos contra el parásito, solo si se administran por periodos prolongados; sin embargo existe el inconveniente de que pueden causar efectos adversos en el hospedero. El objetivo de este trabajo fue evaluar el efecto terapéutico del medicamento OXAL® (albendazol/quinfamida) contra la infección por T. spiralis en modelo murino, durante la fase intestinal de la infección (1 y 7 días) por un periodo de 3 días. Los resultados obtenidos mostraron que la administración de OXAL® durante 3 días, tuvo eficacia terapéutica durante la fase intestinal, ya que no se obtuvo carga parasitaria en el grupo con 1 día de infección, y la obtenida en el grupo con 7 días de infección tuvo una disminución significativa respecto al control, p < 0.05

Trichinellosis is a parasitic disease caused by the nematode Trichinella spiralis. Currently the treatment for Trichinellosis includes the administration of albendazole or mebendazole. These drugs are effective against the parasite, only if administered for prolonged periods; however there is a drawback that can cause adverse effects on the host. The aim of this study was to evaluate the therapeutic efficacy OXAL® (albendazole/quinfamide) against infection by T. spiralis in mice during the intestinal phase of the infection (1, and 7 days) for a period of 3 days. The results showed that administration of OXAL® for 3 days, had effective therapy for intestinal phase, since there was no parasitic load in the group with 1 day of infection, and the obtained in the group with 7 days of infection showed a significant decrease with regard to control, p <0.05