Food-grade titanium dioxide (TiO₂) containing a nanoscale particle fraction (TiO₂-NPs) is approved as a white pigment (E171 in Europe) in common foodstuffs, including confectionary. There are growing concerns that daily oral TiO₂-NP intake is associated with an increased risk of chronic intestinal inflammation and carcinogenesis. In rats orally exposed for one week to E171 at human relevant levels, titanium was detected in the immune cells of Peyer’s patches (PP) as observed with the TiO₂-NP model NM-105. Dendritic cell frequency increased in PP regardless of the TiO₂treatment, while regulatory T cells involved in dampening inflammatory responses decreased with E171 only, an effect still observed after 100 days of treatment. In all TiO₂-treated rats, stimulation of immune cells isolated from PP showed a decrease in Thelper (Th)-1 IFN-γ secretion, while splenic Th1/Th17 inflammatory responses sharply increased. E171 or NM-105 for one week did not initiate intestinal inflammation, while a 100-day E171 treatment promoted colon microinflammation and initiated preneoplastic lesions while also fostering the growth of aberrant crypt foci in a chemically induced carcinogenesis model. These data should be considered for risk assessments of the susceptibility to Th17-driven autoimmune diseases and to colorectal cancer in humans exposed to TiO₂from dietary sources.

Deoxynivalenol (DON) is a mycotoxin produced by Fusarium species which is commonly found in temperate regions worldwide as a natural contaminant of cereals. It is of great concern not only in terms of economic losses but also in terms of animal and public health. The digestive tract is the first and main target of this food contaminant and it represents a major site of immune tolerance. A finely tuned cross-talk between the innate and the adaptive immune systems ensures the homeostatic equilibrium between the mucosal immune system and commensal microorganisms. The aim of this study was to analyze the impact of DON on the intestinal immune response. Non-transformed intestinal porcine epithelial cells IPEC-1 and porcine jejunal explants were used to investigate the effect of DON on the intestinal immune response and the modulation of naive T cells differentiation. Transcriptomic proteomic and flow cytometry analysis were performed. DON induced a pro-inflammatory response with a significant increase of expression of mRNA encoding for IL-8, IL-1α and IL-1β, TNF-α in all used models. Additionally, DON significantly induced the expression of genes involved in the differentiation of Th17 cells (STAT3, IL–17A, IL-6, IL-1β) at the expenses of the pathway of regulatory T cells (Treg) (FoxP3, RALDH1). DON also induced genes related to the pathogenic Th17 cells subset such as IL–23A, IL-22 and IL-21 and not genes related to the regulatory Th17 cells (rTh17) such as TGF-β and IL-10. DON triggered multiple immune modulatory effects which could be associated with an increased susceptibility to intestinal inflammatory diseases.

Epidemiology evidenced the Bisphenol A (BPA), a chemical found in daily consumer products, as an environmental contributor to obesity and type II diabetes (T2D) in Humans. However, the BPA-mediated effects supporting these metabolic disorders are still unknown. Knowing that obesity and T2D are associated with low-grade inflammation and gut dysbiosis, we performed a longitudinal study in mice to determine the sequential adverse effects of BPA on immune system and intestinal microbiota that could contribute to the development of metabolic disorders. We observed that perinatal exposure to BPA (50 µg/kg body weight/day) induced intestinal and systemic immune imbalances at PND45, through a decrease of Th1/Th17 cell frequencies in the lamina propria concomitant to an increase of splenic Th1/Th17 immune responses. These early effects are associated with an altered glucose sensitivity, a defect of IgA secretion into faeces and a fall of faecal bifidobacteria relative to control mice. Such BPA-mediated events precede infiltration of pro-inflammatory M1 macrophages in gonadal white adipose tissue appearing with ageing, together with a decreased insulin sensitivity and an increased weight gain. Our findings provide a better understanding of the sequential events provoked by perinatal exposure to BPA that could support metabolic disorder development in later life.

Background: Bisphenol A (BPA), one of the highest-volume chemicals produced worldwide, has been identified as an endocrine disruptor. Many peer-reviewing studies have reported adverse effects of low dose BPA exposure, particularly during perinatal period (gestation and/or lactation). We previously demonstrated that perinatal oral exposure to BPA (via gavage of mothers during gestation and lactation) has long-term consequences on immune response and intestinal barrier functions. Due to its adverse effects on several developmental and physiological processes, BPA was removed from consumer products and replaced by chemical substitutes such as BPS or BPF, that are structurally similar and not well studied compare to BPA. Here, we aimed to compare perinatal oral exposure to these bisphenols (BPs) at two doses (5 and 50 μg/kg of body weight (BW)/day (d)) on immune response at intestinal and systemic levels in female offspring mice at adulthood (Post Natal Day PND70). Methods: Pregnant female mice were orally exposed to BPA, BPS or BPF at 5 or 50 μg/kg BW/d from 15th day of gravidity to weaning of pups at Post-Natal Day (PND) 21. Humoral and cellular immune responses of adult offspring (PND70) were analysed at intestinal and systemic levels. Results: In female offspring, perinatal oral BP exposure led to adverse effects on intestinal and systemic immune response that were dependant of the BP nature (A, S or F) and dose of exposure. Stronger impacts were observed with BPS at the dose of 5 μg/kg BW/d on inflammatory markers in feces associated with an increase of anti-E. coli IgG in plasma. BPA and BPF exposure induced prominent changes at low dose in offspring mice, in term of intestinal and systemic immune responses, provoking an intestinal and systemic Th1/Th17 inflammation. Conclusion: These findings provide, for the first time, results of long-time consequences of BPA, S and F perinatal exposure by oral route on immune response in offspring mice. This work warns that it is mandatory to consider immune markers and dose exposure in risk assessment associated to new BPA’s alternatives.

This study shows that high pathogenic H5N1 influenza virus infection of chicken induced high levels of bioactive interferon type I in the lung (4.3 × 10⁵ U/mg tissue), plasma (1.1 × 10⁵ U/mL), and spleen (9.1 × 10⁵ U/mg tissue). In contrast, a low pathogenic attenuated H5N1 vaccine strain only induced approximately 24 times less IFN in the lung, 441 times less in the spleen and 649 less in the plasma. This was in the same range as a reassortant carrying the HA from the vaccine strain and the remaining genes from the high pathogenic virus. On the other hand, a reassortant virus with the HA from the high pathogenic H5N1 with the remaining genes from the vaccine strain had intermediate levels of IFN. The level of interferon responses related to the viral load, and those in the spleen and blood to the spread of virus to lymphoid tissue, as well as disease severity. In vitro, the viruses did not induce interferon in chicken embryonic fibroblasts, but high levels in splenocytes, with not clear relationship to pathogenicity and virulence. This, and the responses also with inactivated viruses imply the presence of plasmacytoid dendritic cell-like leukocytes within the chicken immune system, possibly responsible for the high interferon responses during H5N1 infection. Our data also indicate that the viral load as well as the cleavability of the HA enabling systemic spread of the virus are two major factors controlling systemic IFN responses in chicken.