deep-dermal-injection-as-model-candida-albicans-skin-infection-for

Deep Dermal Injection As a Model of <em>Candida albicans</em> Skin Infection for Histological Analyses

The skin is an extremely extended organ of the body and, due to this large surface, it is continuously exposed to microorganisms. Skin damage can easily ...

University of Milano-Bicocca

Chronic inflammation is one of the causes of neurodegeneration in Amyotrophic lateral sclerosis (ALS). Here we examined whether circulating dendritic cells (DCs) can contribute to disease progression. We found ALS patients show a significant reduction in the number of circulating DCs. Also, patients' DCs present an increased expression of CD62L and a tendency to overexpress CCR2 compared with healthy donors. Moreover, DCs derived from a subpopulation of ALS patients produced higher levels of IL-8 and CCL-2 upon lipopolysaccharide (LPS)-stimulation. Finally, we found a significant inverse correlation between the time from onset of the pathology to its diagnosis and the levels of IL-6 secretion induced by LPS. Our data support the hypothesis, in a subpopulation of patients, DCs recruited at the diseased tissue produce high levels of CCL-2 and IL-8 and contribute to the inflammatory process promoting the recruitment of other inflammatory cells. An increased efficiency of IL-6 production may accelerate only the initial phases of disease progression. Blood DC analysis can be used to identify ALS patients with an altered course of inflammatory cell recruitment at the diseased central nervous system (CNS). The high levels of CD62L expression suggests this molecule could be a target for treatment of CNS inflammation.

Inflammatory role of dendritic cells in Amyotrophic Lateral Sclerosis revealed by an analysis of patients' peripheral blood.

Nuclear factor of activated T cells (NFAT) is activated in innate immune cells downstream of pattern recognition receptors, but little is known about NFAT's functions in innate immunity compared with adaptive immunity. We show that early activation of NFAT balances the two major phases of the innate response to  skin infections: the protective containment (abscess) and the elimination (expulsion) phases. During the early containment phase, transforming growth factor- (TGF-) induces the deposit of collagen around newly recruited polymorphonuclear cells to prevent microbial spreading. During the elimination phase, interferon- (IFN-) blocks differentiation of fibroblasts into myofibroblasts by antagonizing TGF- signaling. IFN- also induces the formation of plasmin that, in turn, promotes abscess capsule digestion and skin ulceration for microbial discharge. NFAT controls innate IFN-γ production and microbial expulsion. This cross-talk between the innate immune and the fibrinolytic systems also occurs during infection with  and is a protective response to minimize tissue damage and optimize pathogen elimination.

Article	Year
Inflammatory role of dendritic cells in Amyotrophic Lateral Sclerosis revealed by an analysis of patients' peripheral blood. Scientific reports\| PubMed ID: 28798369	2017
Skin infections are eliminated by cooperation of the fibrinolytic and innate immune systems. Science immunology\| PubMed ID: 28939652	2017

William Santus

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