Neonatal maternal deprivation promotes Nippostrongylus brasiliensis infection in adult rats

https://doi.org/10.1016/j.bbi.2005.07.003Get rights and content

Abstract

Neonatal stress is known to alter immune responses in adults and parasitic infection is modulated by the immune status of the host. The present study aimed to establish whether neonatal maternal deprivation affects the time course of Nippostrongylus brasiliensis infection and associated intestinal alterations in adult rats. Rat pups were separated from their dam 3 h daily during postnatal days 2–14, or left undisturbed. At 12 weeks of age, N. brasiliensis infection was induced by subcutaneous administration of 3000 L3 larvae. At 7 and 12 days after primary infection, the number of intestinal adult worms, fecal egg output, jejunal paracellular permeability, and myeloperoxidase (MPO) activity were measured. On days 7 and 12 after a secondary infection, numbers of adult worms and egg production were determined. Maternal deprivation increased the number of jejunal adult worms and fecal eggs and larvae on day 7 after primary infection, and exacerbated the increase in jejunal MPO activity induced by the infection. On day 12, adult worms were only observed in deprived rats. N. brasiliensis infection did not potentiate the increase in jejunal paracellular permeability induced by maternal deprivation. After the second infection, no egg was detected in both control and deprived rats. In conclusion, maternal deprivation in rats facilitates primary infection by N. brasiliensis and enhances the inflammatory response of the jejunum, but does not induce severe breakdown of immunity to N. brasiliensis.

Introduction

Neonatal stress is known to alter immune responses in adults (Neveu et al., 1994). In rats, maternal deprivation of pups has long-lasting consequences on macrophage activity and on susceptibility to experimental autoimmune encephalomyelitis (Teunis et al., 2002). Thus, neonatal stress enhances the release of Th1 cytokines and decreases the release of Th2 cytokines from splenocytes in adult mice (Loizzo et al., 2002). In rat colon, liver, and spleen neonatal maternal deprivation increases the expression of several cytokines such as IFN-γ, IL-1β, IL-2, IL-4, or IL-10, independently of their Th1 or Th2 status (Barreau et al., 2004). Moreover, maternal deprivation induces alterations in the colonic epithelium, such as an increase of myeloperoxidase activity, mast cell hyperplasia, and increase in paracellular epithelial permeability associated with bacterial translocation (Barreau et al., 2004).

Acquisition of immunity towards parasites depends upon genetic and environmental factors (Gray and Gill, 1993). Among these, the peripartum period seems to be crucial. For example, a high infection rate by giardia has been found in nursing mares, suggesting a periparturient depression of immunity (Xiao and Herd, 1994). A breakdown of immunity to the nematode Nippostrongylus brasiliensis has been recently reported in lactating rats (Houdijk et al., 2003).

It is well known that helminth infection induces a Th2 immune response (Coffman et al., 1989), and data indicate that this response could be responsible for further allergic or autoimmune diseases (Wilson and Maizels, 2004). A major manifestation of acquired immunity to gastrointestinal nematodes is failure of infective larvae to establish and mature into adults in the gut. In rodents, a second challenge with larvae of worms such as Strongyloides venezuelensis or N. brasiliensis is usually sterile with no egg output in the feces and no development of adult worms in the intestine. Infective larvae following challenge are destroyed at the tissue migratory stage, with few larvae surviving the transition from the subcutaneous infection site to the lungs (Dent et al., 1997, Korenaga et al., 1991, Sato and Toma, 1990). On the contrary, it is not clear whether previous non-parasitic immune alterations may affect helminth infection. We hypothesize that neonatal stress may modulate helminth infection in the adult. This hypothesis is reinforced by the facts that neonatal stress affects the response of the hypothalamic–pituitary–adrenocortical (HPA) axis (Biagini et al., 1998) and that HPA axis hormones play a role in regulating the course of parasitic infection (Morales-Montor et al., 2001). Consequently, this study was undertaken to determine whether neonatal maternal deprivation alters the course of N. brasiliensis infection in adult rats and whether it modifies the digestive tract alterations induced by this helminth.

Section snippets

Animals

Primiparous pregnant female Wistar rats were individually housed in standard polypropylene cages containing 2.5 cm of wood chip bedding material. They were kept at a constant temperature room (23 ± 1 °C) and maintained on a 12/12 h light/dark cycle (lights on at 7:00). Food (UAR pellets, Epinay, France) and water were available ad libitum. Mothers and their pups, and then the young rats after weaning on day 22, were kept in the same conditions. All experimental protocols described in this study

Nippostrongylus brasiliensis life cycle

In control rats, 7 days after N. brasiliensis primary infection, the total number of adult worms in the small intestine was 536 ± 54, most of the worms (56.0%) being localized in the proximal jejunum. On the 12th day after infection, no adult worm was detected (Table 1). Similarly, no adult worm was found on days 7 and 12 after the secondary infection. In maternally deprived rats, the number of adult worms in the small intestine on the 7th day after primary infection was increased by 50.2%, in

Discussion

Our results indicate that neonatal maternal deprivation in rats both facilitates a primary infection by N. brasiliensis, since the number of adult worms in the intestine was increased by 50% compared to non-deprived rats, and exacerbates the intestinal inflammation induced by the parasite. However, the breakdown of immunity does not appear to be severe, since no worms survived and intestinal damage was not observed after a secondary infection in maternally deprived rats.

Nippostrongylus

Acknowledgments

The authors acknowledge the financial support of INRA and Fondation pour la Recherche Médicale (FRM).

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