Impairment of Host Resistance to Helminthes with Age in Murine Small Intestine

Abstract

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.

Cytokine elevation in the mouse small intestine at the early stage of infection with the gastrointestinal parasite <i>Heligmosomoides polygyrus</i>

“…2B-C). However, the accumulation of CD4+ T cells was less than the number of CD4+ T cells at Day 8, which was demonstrated in a previous report [13]. No cysts were found on the second day; therefore, no cell accumulation was observed (data not shown), suggesting that the CD4+ T cells started to accumulate because the larvae were embedded in the muscle layer.…”

“…In mice, primary inoculation with Hp is associated with chronic infection because the initial elevation in type-2 cytokine production is not enough to eliminate the worms. However, after the parasite is cleared from the mouse with an antihelminthic drug such as pyrantel pamoate, subsequent reinfection with Hp results in a quick and strong memory response, with worm expulsion observed by about 12 days after reinfection [1,2,13]. In a previous study, our results indicated that the quick migration of CD4+ T cells to the host-parasite interface under the mucosa results in a strong Th2 response at the early stage after a challenge [14].…”

“…reported an elevation in type-2 cytokines from Day 5 after Hp infection [ 18 ]. Our previous results also indicated that the level of type-2 cytokine gene expression through Day 4 after infection remained unchanged, with an increase observed after Day 4 [ 13 , 14 ]. From this previous study, we confirmed that CD4+ T cells had become activated and migrated to the cyst area by Day 8 after infection, but these processes had not yet occurred at Day 4.…”

Regulation of type 2 diabetes by helminth-induced Th2 immune response

“…Previous studies have shown that expression of type 2 cytokines is markedly elevated at Day 8 after Hp infection in BALB/c mice [31]. However, the peak was lower in C3H/HeN and C57BL/6J mice than in BALB/c mice.…”

The Effect of Radiation on the Immune System in Pigs Affected by the Fukushima Daiichi Nuclear Power Plant Accident

“…11.1b, some abandoned pigs were infected with T. suis, which does not normally cause severe symptoms in the host. In general, nematode infection usually induces Th2 cytokines in the host [27][28][29], but we did not detect any elevation of IL-4 and IL-10 in abandoned pigs (data not shown). Therefore, we considered that the increase of IFN-γ gene expression in abandoned pigs was not due to parasitic infection.…”