Role of mucosal dendritic cells in inflammatory bowel disease

The gastrointestinal innate and adaptive immune system continuously faces the challenge of potent stimuli from the commensal microflora and food constituents. These local immune responses require a tight control, the outcome of which is in most cases the induction of tolerance. Local T cell immunity is an important compartment of the specif ic intestinal immune system. T cell reactivity is programmed during the initial stage of its activation by professional presenting cells. Mucosal dendritic cells (DCs) are assumed to play key roles in regulating immune responses in the antigen-rich gastrointestinal environment. Mucosal DCs are a heterogeneous population that can either initiate (innate and adaptive) immune responses, or control intestinal inflammation and maintain tolerance. Defects in this regulation are supposed to lead to the two major forms of inflammatory bowel disease (IBD), Crohn's disease (CD) and ulcerative colitis (UC). This review will discuss the emerging role of mucosal DCs in regulating intestinal inflammation and immune responses.

Overexpression of Toll-like receptor 4 contributes to the internalization and elimination of Escherichia coli in sheep by enhancing caveolae-dependent endocytosis

Background:Gram-negative bacterial infections have a major economic impact on both the livestock industry and public health.Toll-like receptor 4(TLR4)plays a crucial role in host defence against Gram-negative bacteria.Exploring the defence mechanism regulated by TLR4 may provide new targets for treatment of inflammation and control of bacterial infections.In a previous study,we generated transgenic sheep overexpressing TLR4 by microinjection to improve disease resistance.The defence mechanism through which TLR4 overexpression protected these sheep against pathogens is still not fully understood.Results:In the present study,we used Escherichia coli to infect monocytes isolated from peripheral blood of the animal model.The overexpression of TLR4 strongly enhanced the percentage of endocytosis and capacity of elimination in monocytes during the early stages of infection.This phenomenon was mainly due to overexpression of TLR4 promoting caveolae-mediated endocytosis.Pretreatment of the transgenic sheep monocytes with inhibitors of TLR4,Src signalling,or the caveolae-mediated endocytosis pathway reduced the internalization of bacteria,weakened the ability of the monocytes to eliminate the bacteria,and increased the pH of the endosomes.Conclusion:Together,our results reveal the effects of TLR4 on the control of E.coli infection in the innate immunity of sheep and provide crucial evidence of the caveolae-mediated endocytosis pathway required for host resistance to invading bacteria in a large animal model,providing theoretical support for breeding disease resistance in the future.Furthermore,Src and caveolin 1(CAV1)could be potentially valuable targets for the control of infectious diseases.

No plant functional diversity effects on foliar fungal pathogens in experimental tree communities

Foliar fungal pathogens affect forest ecosystem processes by exerting highly species-specific impacts on growth and survival of trees.As many ecosystem processes in forests depend on functional diversity of specific tree species,a close relationship is expected between this and foliar fungal pathogen infestation.Testing for such a relationship in the German tree diversity experiment BIOTREE(Bechstedt),we hypothesized that pathogen richness and pathogen load decline with increasing functional diversity of tree communities.Using macro-and microscopic analyses,we assessed pathogen richness and load on 16 tree species in plots that,although differing in functional diversity,had the same tree species richness.We found no effects of functional diversity on pathogen richness or load.However,we encountered strong species identity effects in plot species composition,as susceptible tree species contributed positively to each community’s pathogen richness and load.Furthermore,testing for effects of particular leaf traits and geographical range size of host species revealed a significant effect of total leaf phenolics,which was unexpected as pathogen richness increased with increasing content in polyphenolics.Our study showed that at the community level,host species’identity was more important for foliar fungal pathogen richness and load than the functional diversity of host trees.The positive relationship between pathogen richness and phenolics in leaves,along with the finding that pathogen richness is very much conserved in tree species,point to an evolutionary arms race between hosts and fungi resulting from fungi increasing their capacity to infect tree leaves and trees boosting their defences.