An inherent elevation in type 2 immunity is a feature of maternal and offspring immune systems. This has diverse implications for maternal and offspring biology including influencing success of pregnancy, offspring immune development and maternal and offspring ability to control infection and diseases such as allergies. In this review we provide a broad insight into how this immunological feature of pregnancy and early life impacts both maternal and offspring biology. We also suggest how understanding of this axis of immune influence is and may be utilised to improve maternal and offspring health.

Some oligosaccharides induce growth of anti-inflammatory bacterial species and induce regulatory immunity in humans as well as animals. We have shown that the equine gut microbiota and the immune-microbial homeostasis largely stabilize within the first 50 days of life. Furthermore, we have previously established that certain bacterial species in the equine gut correlated with regulatory immunity. Accordingly, we hypothesized that an oligosaccharide rich diet fed to foals during the first 50 days would increase the abundance of bacterial species associated with regulatory immunity, and that this would influence immune responses in the foals. Eight pregnant mares and their foals were fed an oligosaccharide rich diet from 4 weeks before expected parturition until 49 days post-partum. Six mares and foals served as control. Fecal microbiota from mares and foals was characterized using 16S rRNA gene amplicon high throughput sequencing. On Day 49 the test foals had significantly higher abundances of Akkermansia spp. Blood sampled from the foals in the test group on Day 7, 28, and 49 showed non-significant increases in IgA, and decreases in IgG on Day 49. In BALB/cBomTac mice inoculated with gut microbiota from test and control foals we found increased species richness, increased relative abundance of several species identified as potentially anti-inflammatory in horses, which were unclassified Clostridiales, Ruminococcaceae, Ruminococcus, Oscilospira, and Coprococcus. We also found increased il10 expression in the ileum if inoculated with test foal microbiota. We conclude that an oligosaccharide diet fed to foals in the \"window of opportunity,\" the first 50 days of life, increases the abundance of anti-inflammatory species in the microbiota with potentially anti-inflammatory effects on regulatory immunity.

Administration of inactivated probiotics has been proved to enhance host immunity. Herein, we aim to explore their potential in modulating systemic autoimmune disorders. The bovine type II collagen (CII)-induced arthritis (CIA) and CII antibody-induced arthritis (CAIA) mice models were used in this study. Heat-killed Lactobacillus reuteri (h-L. reuteri) was administered before or after the induction of CIA. The results indicated that the severity of CIA was alleviated and the prevalence of CIA was decreased in the mice pre-treated with h-L. reuteri. Using enzyme-linked immunosorbent assays, we found that decreased serum CII-specific IgG antibody IL-6 and CXCL1 but the increased level of IL-10 was found in h-L. reuteri-treated cohort. Moreover, h-L. reuteri treatment decreased the severity and incidence of arthritis in the CAIA model which was associated with a early decrease of IL-6. Systematic supplement of exogenous IL-6 reversed h-L. reuteri-induced CIA suppression. For regulatory immune responses, the frequency of Tregs and CD4+IL-10+ cells was increased in the draining lymph of joint of h-L. reuteri-treated mice after second immunization. Parallelly, we found that if CIA was induced, CD103+ dendritic cells in mesenteric lymph nodes and α4β7+ Tregs in the spleen were increased in h-L. reuteri-treated mice, suggesting h-L. reuteri might affect the peripheral migration of Tregs to modulating CIA. Finally, the mice with progressive CIA were treated with h-L. reuteri after the second immunization. No alleviation of CIA severity, as well as an increase of splenic α4β7+ Tregs, was observed in these mice. This study indicates that pre-administration of h-L. reuteri can alleviate the CIA in mice and may serve as a promising strategy for autoimmune disease prevention.

Leishmania donovani exposure often results in subclinical infection in immunocompetent individuals, and the factors dictating development of visceral leishmaniasis (VL) are not known. Infection with intestinal worms skew immunity towards type 2 and regulatory responses, thereby theoretically increases susceptibility to intracellular infections controlled by type 1 responses. Here we have tested how chronic infection with the intestinal nematode Heligmosomoides polygyrus affected immunity to a secondary infection with L donovani. We found that mice infected with H polygyrus displayed higher Leishmania burden in liver and spleen compared to worm-free animals. This increased infectious load was accompanied by reduced leucocyte infiltration and nos2 transcription in livers and increased il4 and il10 transcription in spleens. Collectively, these data show that chronic infection with intestinal nematodes skew immune responses in a way that may favour development of VL.

Gut microbiota regulated imbalances in the host\'s immune profile seem to be an important factor in the etiology of type 1 diabetes (T1D), and identifying bacterial markers for T1D may therefore be useful in diagnosis and prevention of T1D. The aim of the present study was to investigate the link between the early gut microbiota and immune parameters of non-obese diabetic (NOD) mice in order to select alleged bacterial markers of T1D. Gut microbial composition in feces was analyzed with 454/FLX Titanium (Roche) pyro-sequencing and correlated with diabetes onset age and immune cell populations measured in diabetic and non-diabetic mice at 30 weeks of age. The early gut microbiota composition was found to be different between NOD mice that later in life were classified as diabetic or non-diabetic. Those differences were further associated with changes in FoxP3(+) regulatory T cells, CD11b(+) dendritic cells, and IFN-γ production. The model proposed in this work suggests that operational taxonomic units classified to S24-7, Prevotella, and an unknown Bacteriodales (all Bacteroidetes) act in favor of diabetes protection whereas members of Lachnospiraceae, Ruminococcus, and Oscillospira (all Firmicutes) promote pathogenesis.