Wednesday, September 16, 2015

Pain sensing neurons alert dendritic cells for presence of skin fungal parasites

IL-23/IL-17 axis plays important role in the host's defense against fungal parasites. Recent studies show that skin CD11bdendritic cells and skin γδ T cells contribute for anti-fungal protection.

Using mouse model of candida albicans fungal infection, the authors first re-confirmed that cytokine IL-17 showed anti-fungal activity.

Next, the authors showed that the source of this protective IL-17 were skin γδ T cells (and not conventional αβ T cells or non-conventional dendritic epidermal T cells (DETCs).

Next, the authors re-confirmed that IL-23 was upstream of IL-17 in host's protection against candida albicans fungal infection.

Next, the authors showed that skin langerhans cells (LCs) and Batf3 + CD103+ DCs (LCΔ Batf3 Δ) were dispensable for anti-fungal protection.

However, the authors found that IL-23 derived from C-type lectin positive dermal DCs (using Mgl2-DTR + IL-23KO BM chimera) were necessary for this protection.

Afterwards, the authors found that ablation of skin nociceptors, TRPV1, decreased anti-fungal protection.

Finally, the authors found that upon detection of candida albicans, CGRP (calcitonin gene related peptide) secreted by TRPV1 neurons acted on Mgl2+ dermal DCs to induce IL-23 secretion that in turn induce protective IL-17 from local skin γδ T cells (strangely, however, Fig. 6H and 6I do not match the authors text in the results. Here, -DT+CGRPα samples should have significantly lower CFU compared to +DT+CGRPα samples, since DT depletes Mgl2+ DCs).

In summary, these results provide additional support for neuro-immune network affecting host's protection against infection. This does not mean that neurons are important for ultimate clearance of the pathogen. Here, the authors only showed day 3 of infection when there is a maximum burden of fungal pathogen.

However, there is also a broader implications. Mainly, how CNS can influence or even imitate local immune response and produce or augment skin inflammation such as in psoriasis, dermatitis, eczema, urticaria and skin allergies.  

David Usharauli

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