The purpose of this study was to investigate the ultrastructure of the extracellular matrix of human cornea and sclera by using the atomic force microscope (AFM). Specimens of human cornea (n=16) and sclera (n=10) were obtained from a cornea bank or from enucleated eyes (n=1; clinical and histopathological diagnosis: choroidal melanoma) and fixed in Karnovsky solution. The AFM resolved individual collagen fibrils in corneal and scleral tissue. Scleral collagen fibrils had a diameter ranging from 118.3 to 1268.0 nm and showed clear banding with a mean axial D-periodicity of 77.02 nm. The mean gap depth between the two overlaps was larger in the sclera than in the cornea. The diameter of corneal collagen fibrils ranged from 48.0 to 113.0 nm. In contrast to the sclera, the corneal collagen fibrils did not exhibit clear banding as their surface pattern. Closely attached fibrils with a beaded to globular structure were predominant in the cornea. The mean axial D-periodicity of the corneal collagen fibrils was 68.50 nm. In both tissues, the AFM resolved structures resembling cross-bridges between adjacent fibrils. The corneal collagen fibrils showed fibrillar properties that were different from those of the sclera, and that therefore might be essential for the spatial organization responsible for the optical quality of the cornea.

Our results suggest that induction of a LPS-tolerant state in antigen-presenting cells (APCs) may contribute to the protective effect of a farming environment. TLR2 agonists similar to those appearing in cowshed dust extracts, such as our synthetic LPGerD, lead to the ignorance of the LPS stimulus, which is important for the activation of APCs to mount a Th2 immune response. This substance might be a promising candidate for allergy-preventive treatments as LPGerD had only low pro-inflammatory characteristics.

Since the first description of dendritic cells by Steinman and Cohn in 1973, this important cell type has gained increasing attention. Over 4000 papers have been published on this topic annually during the last few years. At the beginning, dendritic cells were recognized for their immune stimulatory properties and their importance in initiating an adaptive immune response. Later, it was found that dendritic cells do not only initiate but also regulate immune responses. This attribute makes the so-called regulatory dendritic cells highly important for the prevention of exaggerated immune responses. Immune cells make contact with different Ags every day and must be tightly controlled to prevent excessive inflammation and subsequent organ destruction, particularly in organs such as the gut and lungs. Here, we give a brief overview of our current knowledge on how immune responses are controlled by dendritic cells, highlighting how they are involved in the induction of peripheral tolerance. We focus on what is known about these processes in the lung, with a closer look at their role in the induction and control of diseases such as bronchial asthma, chronic obstructive pulmonary disease and lung infections. Finally, we summarize some current approaches to modulate the behavior of dendritic cells that may hopefully lead to future therapeutics to control exaggerated immune responses.

Arabinogalactan (AG) isolated from dust of a traditional farm prevents disease in murine models of allergy. However, it is unclear whether this polysaccharide has immune regulatory properties in humans. The aim of this study was to test the influence of AG on the immune-stimulating properties of human dendritic cells (DCs). Moreover, we sought to identify the receptor to which AG binds. AG was produced from plant callus tissue under sterile conditions to avoid the influence of pathogen-associated molecular patterns in subsequent experiments. The influence of AG on the human immune system was investigated by analyzing its impact on monocyte-derived DCs. To analyze whether the T cell stimulatory capacity of AG-stimulated DCs is altered, an MLR with naive Th cells was performed. We revealed that AG reduced T cell proliferation in a human MLR. In the search for a molecular mechanism, we found that AG binds to the immune modulatory receptors DC-specific ICAM-3–grabbing non integrin (DC-SIGN) and macrophage mannose receptor 1 (MMR-1). Stimulation of these receptors with AG simultaneously with TLR4 stimulation with LPS increased the expression of the E3 ubiquitin-protein ligase tripartite motif–containing protein 21 and decreased the phosphorylation of NF-κB p65 in DCs. This led to a reduced activation profile with reduced costimulatory molecules and proinflammatory cytokine production. Blocking of MMR-1 or DC-SIGN with neutralizing Abs partially inhibits this effect. We conclude that AG dampens the activation of human DCs by LPS via binding to DC-SIGN and MMR-1, leading to attenuated TLR signaling. This results in a reduced T cell activation capacity of DCs.

More than fifty c-type lectin receptors (CLR) are known and have been identified so far. Moreover, we know the group of galectins and sialic acid-binding immunoglobulin-type lectins that also belong to the carbohydrate-binding receptors of the immune system. Thus, the lectin receptors form the largest receptor family among the pathogen recognition receptors. Similar to the toll-like receptors (TLRs), the CLR do not only recognize foreign but also endogenous molecules. In contrast to TLRs, which have a predominantly activating effect on the immune system, lectin receptors also mediate inhibitory signals. They play an important role in innate and adaptive immunity for the induction, regulation and shaping of the immune response. The hygiene hypothesis links enhanced infection to protection from allergic disease. Yet, the microbial substances that are responsible for mediating this allergy-protective activity still have to be identified. Microbes contain both ligands binding to TLRs and carbohydrates that are recognized by CLR and other lectin receptors. In the current literature, the CLR are often recognized as the ‘bad guys’ in allergic inflammation, because some glycoepitopes of allergens have been shown to bind to CLR, facilitating their uptake and presentation. On the other hand, there are many reports revealing that sugar moieties are involved in immune regulation. In this review, we will summarize what is known about the role of carbohydrate interaction with c-type lectins and other sugar-recognizing receptors in anti-inflammation, with a special focus on the regulation of the allergic immune response.