Characterization of Clinical and Immune Response in a Rotavirus Diarrhea Model in Suckling Lewis Rats

Abstract

Group A rotaviruses (RVs) are the leading pathogens causing diarrhea in children and animals. The present study was designed to establish an experimental model of RV infection and immune response in suckling rats. Wistar (W) and Lewis (L) suckling rats were inoculated orally with two different doses of a simian RV SA-11 strain. RV infection was evaluated by growth rate and clinical indexes. Virus-shedding and serum anti-RV antibodies were measured by enzyme-linked immunosorbent assay (ELISA). Mucosal interferon-␥ (IFN␥), specific splenocyte proliferation, and spleen and intestinal intraepithelial lymphocyte (IEL) phenotype were analyzed. No diarrhea was observed in any inoculated Ws. All Ls developed acute moderate diarrhea, and a high score and incidence of diarrhea were found in rats infected with higher titers of RV. Specific humoral and cell systemic immune response was confirmed by splenocyte proliferation and by the presence of serum anti-RV antibodies. Moreover, RV infection induced changes in IEL composition, which showed an increase in the proportion of innate immune cells with respect to cells involved in acquired immunity. This acute moderate diarrhea process constitutes a good experimental model that also provides some immune biomarkers that may allow establishing modulation by drugs or diet components.

Preclinical Immunomodulation by the Probiotic Bifidobacterium breve M-16V in Early Life

“…The design chosen was that in which the cells from the immune system compartments are still in development (age comprised during the suckling period of the animals) [31–37], but without the interference of breast milk compounds (forcing transition to solid diet on day 17 of life). Moreover, in order to avoid the transitional trapping lymphocytes effects of weaning on immune system [38], last day of experiment was performed on day 19, two days after early weaning.…”

“…Faecal samples were scored from 1 to 4 (faecal appearance score [FAS]) based on colour, texture and amount as described: normal faeces (1); soft yellow-green faeces (2); totally loose yellow-green faeces (3); high amount of watery faeces (4). Scores ≥ 2 indicate diarrhoeic faeces [37]. Faecal weight for each specimen obtained was also measured.…”

“…It was cut in 5 mm pieces, weighed, and incubated with phosphate buffer solution for 10 min in a 37°C shaker. After centrifugation, supernatants were stored at -20°C until analysis [37]. …”

The Suckling Rat as a Model for Immunonutrition Studies in Early Life

“…Besides these outcomes, our group has provided a self-limiting acute model that show some of the mechanisms involved in immune protection and resolution of the diarrhea process. It provides some immune response biomarkers, such as lymphocyte phenotype and proliferative ability, which may help to evaluate the activity of several food compounds, not only by shortening the diarrhea process, but also by enhancing the specific RV immune response [115]. …”

Simultaneous Detection of Group A Rotavirus in Swine and Rat on a Pig Farm in Brazil

“…Later, an identification of these viral structural proteins proved to be group B rotavirus [9]. In addition to that, rats have been used as animal model to study pathophysiology of rotavirus infection [10–13]. …”