Helminth-induced type 2 cytokines increase the number of regulatory T cells and
alternatively activated macrophages, resulting in modulation of the host–immune system.
Studies on these parasite-induced immunoregulatory mechanisms might contribute to the
development of new therapies for inflammatory diseases, including type 2 diabetes (T2D).
Previous studies have suggested that progression of obesity-associated metabolic
abnormalities is under pathophysiological control of CD4+ T cells. Glucose absorption
through the intestinal epithelium reduced after infection in a STAT-6-dependent manner. In
this study, we investigated whether infection with the gastrointestinal nematode parasite
Heligmosomoides polygyrus (Hp) can modulate T2D-associated pathology in
a mouse model (KK-Ay/TaJcl). KK-Ay/TaJcl mice were inoculated with infective third-stage
Hp larvae and studied at Day 8 following infection. Uninfected KK-Ay/TaJcl mice showed
high blood glucose levels even 120 min after administration of glucose by IP injection.
However, it was significantly improved in the infected group. HOMA-IR, fat accumulation
and FAS gene expression in the liver were significantly decreased by Hp infection. GLUT2
gene expression in this group was significantly lower than that in the uninfected diabetic
mice, which might be related to the decrease in glucose absorption in the
parasite-infected intestine. In conclusion, helminth-induced type 2 immune responses might
contribute to T2D disease control.
ABSTRACT. This study aims to understand Th2 immune responses and alternative macrophage activation against nematode parasites in aged mice. Eighteen-month (18 M) and three-month (3 M) old C3H/HeN mice were inoculated with Heligmosomoides polygyrus (Hp) larvae. Real-time PCR analysis indicated that interleukin (IL)-4 and IL-13 gene expression was elevated in both groups after infection, but the expression level was significantly low in 18 M mice. Macrophage phenotype was monitored by measuring arginase-1 gene expression and immunofluorescence staining in small intestine, showing a decrease in the number of alternatively activated macrophages (AAMacs) around worm cysts in 18 M mice. These results suggest that the Th2 immune response in aged mice against a nematode parasite was not sufficiently induced to promote AAMacs.
Age-associated alterations of Th2 immune responses against nematode parasites are largely unknown. We investigated primary and memory responses against two types of gastrointestinal nematode parasites, Heligmosomoides polygyrus (Hp) and Nippostrongylus brasiliensis (Nb), in aged mice. The small intestinal gene expression of Th2 cytokines was almost unchanged after primary (Nb and Hp) and secondary infection (Hp) in aged mice in contrast to strongly increased small intestinal gene expression of Th2 cytokines in young (3-month-old) mice. Mucus production decreased (Nb), and worm expulsion was impaired (Nb and Hp) compared with the young mice. Immunofluorescent staining revealed that after Hp infection, the number of alternatively activated macrophages, which are induced by Th2 cytokines, was lower in the aged mice. On the other hand, the number of CD4(+) T cells recruited to the worm cysts was normal compared with the young mice. These results suggest that migration of CD4(+) T cells to the host-parasite interface is not affected by ageing. Alterations in Th2 immune responses in aged mice might be due to inappropriate or insufficient activation of CD4(+) T cells in the submucosa.
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