Malaria is still a life-threatening infectious disease that continues to produce 2 million deaths annually. Malaria parasites have acquired immune escape mechanisms and prevent the development of sterile immunity. Regulatory T cells (Tregs) have been reported to contribute to immune evasion during malaria in mice and humans, suggesting that activating Tregs is one of the mechanisms by which malaria parasites subvert host immune systems. However, little is known about how these parasites activate Tregs. We herein show that TLR9 signaling to dendritic cells (DCs) is crucial for activation of Tregs. Infection of mice with the rodent malaria parasite Plasmodium yoelii activates Tregs, leading to enhancement of their suppressive function. In vitro activation of Tregs requires the interaction of DCs with parasites in a TLR9-dependent manner. Furthermore, TLR9−/− mice are partially resistant to lethal infection, and this is associated with impaired activation of Tregs and subsequent development of effector T cells. Thus, malaria parasites require TLR9 to activate Tregs for immune escape.

Strategies to manipulate the intestinal microbiota have been considered to promote immune health. The aim of the present study was to examine whether fructo-oligosaccharide, a typical prebiotic, could suppress antigen-specific skin inflammation by favourably changing the population of intestinal microbiota. Female BALB/c mice were fed a synthetic diet with or without fructo-oligosaccharide supplementation for 3 weeks and were then epicutaneously immunised with 2,4-dinitrofluorobenzene. Afterwards, mice continued to receive their respective diets. At 5 d after immunisation, the mice were ear challenged with the hapten. Ear swelling after the challenge was significantly reduced in the mice fed the diet supplemented with fructo-oligosaccharide than in mice fed the control diet. To characterise the change in the intestinal microbiota, DNA samples isolated from fresh faeces were subjected to PCR -denaturing gradient gel electrophoresis and real-time PCR based on 16S rDNA gene sequences. Dietary fructo-oligosaccharide altered the composition of intestinal microbiota. The numbers of bifidobacteria, but not lactobacilli, were significantly higher in mice fed the fructo-oligosaccharide-supplemented diet than in mice fed the control diet. Ear swelling was negatively correlated with the numbers of bifidobacteria in the faeces. Sequence analysis revealed that Bifidobacterium pseudolongum was the most predominant bifidobacteria in the intestine of mice fed the fructo-oligosaccharide-supplemented diet. These results suggest that consumption of fructo-oligosaccharide reduces contact hypersensitivity, which is associated with proliferation of B. pseudolongum in the intestinal tract of mice. Prebiotics: Intestinal microbiota: Contact hypersensitivity: MiceAllergic contact dermatitis is one of the most prevalent human skin diseases, causing moderate to severe inflammatory damage. This pathological condition arises after contact hypersensitivity (CHS) (1) . CHS is a T cell-mediated, antigenspecific type of skin inflammation that is induced by topical skin contact with haptens in a previously sensitised host (2,3) . When the host is sensitised by application of the hapten, skin dendritic cells capture the hapten and migrate to draining lymph nodes, where they prime specific T cells. These cells differentiate into CHS effector cells, which recirculate through the blood. The second contact with the same hapten leads to a skin inflammatory response that peaks 24-48 h after challenge. Avoidance of causal allergens is one of the emphasised therapeutic suggestions for CHS; however, avoidance is not practical in the majority of cases.2,4-Dinitrofluorobenzene (DNFB) (4) , picryl chloride (5) and oxazolone (6) have been used as typical haptens, which induce CHS in animals. DNFB-induced CHS in mice is the most widely used animal model for allergic contact dermatitis. In this model, mice are sensitised by application of DNFB onto shaved skin and are ear challenged by application of DNFB. Maximal ear swelling is observed 24 -48 h after challen...