Mouse and human intestinal immunity: same ballpark, different players; different rules, same score

Abstract

The study of animal immune physiology and animal models of human disease have accelerated many aspects of translational research by allowing direct, definitive investigations. In particular, the use of mice has allowed genetic manipulation, adoptive transfer, immunization, and focused cell and tissue sampling, which would obviously be unthinkable for studies in humans. However, the disease relevance of some animal models may be uncertain and difficulties in interpretation may occur as a consequence of immunological differences between the two species. In this review, we will consider general differences in the structure and development of human and mouse mucosal lymphoid microenvironments and then discuss species differences in mucosal B- and T-cell biology that relate to the current concepts of intestinal immune function.

Giardia muris Infection in Mice Is Associated with a Protective Interleukin 17A Response and Induction of Peroxisome Proliferator-Activated Receptor Alpha

“…In the mouse gut, high numbers of CD4 ϩ Th17 cells are already present at steady state. Differentiation of the Th17 cells is directed by retinoic acid-related orphan receptor ROR␥T and driven by the cytokines IL-6 and TGF-␤ (27), all of which were found to have higher gene expression early on in the infection of C57BL/6 mice. In addition, work done by Bienz et al (28) and Zhou et al (29) has revealed that IL-6 plays an important role in controlling acute G. duodenalis infections in mice.…”

Microbial translocation and skeletal muscle in young and old vervet monkeys

“…Walking speed was slower (a; n = 51; p < 0.001), and muscle mass was reduced as measured by leg circumference (b; n = 22, p = 0.05) and by CTdetermined total lean tissue mass measured from both hind limbs (c; n = 27, p = 0.04) in old monkeys. *p < 0.05, ***p < 0.001 2007a; Choi et al, 2012), and this species has comparable intestinal structure and immune function to people (Gibbons and Spencer, 2011). We demonstrate that healthy aging (optimal diet and maintained activity levels) prevents the development of metabolic disease and increases in MT, but does not prevent sarcopenia.…”

The current challenges for vaccine development

“…The expression of TLRs on immune cells such as dendritic cells, which strongly dictate the type of immune response induced, and downstream signalling following TLR activation vary considerably between mice and humans (Mestas & Hughes, 2004;Peng, 2005;von Bernuth et al, 2008). In terms of adaptive immunity, their antibody classes and subclasses do not accurately correspond in terms of function and abundance; for example, high concentrations of IgA1 and IgA2 are present in human serum whilst murine IgA is of a single class and present at very low levels in the serum (Gibbons & Spencer, 2011). There is also evidence to suggest that the polarization of T-helper (Th) cell subsets is not as clear cut in humans as it is in mice, and that regulation of Th differentiation may also be different (Gibbons & Spencer, 2011;Mestas & Hughes, 2004).…”

“…In terms of adaptive immunity, their antibody classes and subclasses do not accurately correspond in terms of function and abundance; for example, high concentrations of IgA1 and IgA2 are present in human serum whilst murine IgA is of a single class and present at very low levels in the serum (Gibbons & Spencer, 2011). There is also evidence to suggest that the polarization of T-helper (Th) cell subsets is not as clear cut in humans as it is in mice, and that regulation of Th differentiation may also be different (Gibbons & Spencer, 2011;Mestas & Hughes, 2004).…”