Role of dendritic cells: a step forward for the hygiene hypothesis

Abstract

The hygiene hypothesis was proposed more than two decades ago, but its mechanism remains unclear. This review focuses on recent advances in the field, especially on the role played by dendritic cells (DCs) and their modulating effects on various infections and allergic diseases, including allergic asthma. DCs isolated from mice long after the resolution of an infection were reported to have a significant modulating effect on allergen-specific Th2 responses in both in vitro and in vivo systems. These DCs showed DC1-like and/or tolerogenic DC capacity, which allowed for the inhibition of allergic responses by immune deviation (enhancing Th1 response) and immune regulation (through regulatory T-cell and Th2 hyporesponsiveness) mechanisms. These findings represented a significant advance in the elucidation of the mechanisms underlying the hygiene hypothesis. Further investigation on the mechanisms by which DCs are 'educated' by infectious agents and the influence of the type, time, and extent of infections on this 'education' process will help us understand immune regulation in disease settings and in the rational design of preventive/therapeutic approaches to allergy/asthma and infections.

The hygiene hypothesis revisited

“…Early infections seem to shape the immune system as compared with more recent illnesses [54]. One answer as to why some classically Th2-skewing parasites induce atopy and others do not is via their ability to induce Treg or another type of IL-10/TGFb-producing cell [55,56].…”

Characterization of the liver-draining lymph nodes in mice and their role in mounting regional immunity to HBV

“…15 Given the above data demonstrating that the liver-draining LNs are vital unclear. In our study, we identified the liver-draining LNs by injection of Evans blue, demonstrating staining of the portal LN by Evans blue at 5 min post-injection and the celiac LN at 8 min (Figure 2a).…”

Multi-target drugs to address multiple checkpoints in complex inflammatory pathologies: evolutionary cues for novel “first-in-class” anti-inflammatory drug candidates: a reviewer’s perspective

“…T helper (T H ) cells such as T H 1, T H 2, T H 17, T reg and antigen-presenting cells (APC), e.g., dendritic cells, monocytes and macrophages [36]. Chronic inflammation involves the differential polarization of T H cells.…”

“…Naïve T H cell activation and polarization into the different subtypes occur in response to at least three stimuli, namely presentation of antigen by APC, co-stimulatory molecules and the cytokine milieu [37]. T H 1 (type 1 immunity against intracellular pathogens such as viruses and cancer cells) relies on IFNc, IL2, IL12 (major T H 1 polarizing cytokines), and T H 2 (type 2 immunity against extracellular pathogens such as multi-cellular parasites) relies on IL4, IL5 [36]. T reg is crucial for suppressing excessive immune responses [38].…”