Healthy Skin Guards Against Infection By Constant Immune Surveillance

Univ.-Prof. Dr. med. Tilo Biedermann Klinikdirektor Klinik und Poliklinik für Dermatologie und Allergologie der Technischen Universität München Biedersteinerstr. MünchenMedicalResearch.com Interview with:
Univ.-Prof. Dr. med. Tilo Biedermann

Klinikdirektor
Klinik und Poliklinik für Dermatologie und Allergologie
der Technischen Universität München
Biedersteinerstr. München

Medical Research: What is the background for this study? What are the main findings?

Prof. Biedermann: The skin is constantly exposed to microbes and skin developed during evolution under the constant influence of microbes. Tightly regulated communication between microbes and the skin can be expected and levels of regulation still needed to be explored. We found that Gram-positive bacteria when sensed by one certain innate immune receptor (hetero dimer TLR 2-6 suppresses immunity both in animal models and in humans. Following the sensing of lipoproteins by toll like receptor 2-6) skin produces high levels of InterleukinL6 that induce the accumulation of so called myeloid-derived suppressor cells. These cells can be found in the blood but also migrate to the skin suppressing T-cell-immunity allowing infections to spread on the skin.

Medical Research: What should clinicians and patients take away from your report?

Prof. Biedermann: Our investigations highlight the importance of even limited skin infections and how important it is to treat both inflammation and infection of the skin. These investigations also highlight that it is not any microbe that regulates this type of immune response but that it needs certain microbes with certain types of ligands that stimulate immunity. Stabilizing healthy skin including the microflora probably best prevents this type of vicious circle of inflammation.

Medical Research: What recommendations do you have for future research as a result of the study?

Prof. Biedermann:
It is very important to understand when induction of myeloid-derived suppressor cells (MDSC) is “good” and when it is “bad” for the host. E.g. by terminating cutaneous inflammation, by regulating excessive immune responses or by supplying important precursor cells for new cutaneous resident immune cells, MSDC exert beneficial functions for the host. On the other hand MDSC suppress immune responses against tumors, against infections, against parasites. These functions are harmful for the host. Questions arise such as “When are these cells bad?” “How can they be regulated, inhibited or avoided?” Aside from understanding the mechanisms of suppressions by myeloid derived suppressor cells, induction and accumulation, and the migration to different tissue sites that we have started to analyze in our publication should be studied in more detail. Targeting the regulation of specific cellular subsets will be a basis for powerful new strategies for immune therapy.

Citation:
Cutaneous Innate Immune Sensing of Toll-like Receptor 2-6 Ligands Suppresses T Cell Immunity by Inducing Myeloid-Derived Suppressor Cell

Yuliya Skabytska,Florian Wölbing,Claudia Günther,Martin Köberle,Susanne Kaesler,Ko-Ming Chen,Emmanuella Guenova,Doruk Demircioglu,Wolfgang E. Kempf,Thomas Volz,Hans-Georg Rammensee,Martin Schaller,Martin Röcken,Friedrich Götz,Tilo Biedermann

DOI: http://dx.doi.org/10.1016/j.immuni.2014.10.00

CellPress Immunity Volume 41, Issue 5, p762–775, 20 November 2014