153 © 2016 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd. | JDDG | 1610-0379/2016/1402 Minireview Submitted: 14.6.2015 Accepted: 4.8.2015 Conflict of interest None. DOI: 10.1111/ddg.12843 How the innate immune system trains immunity: lessons from studying atopic dermatitis and cutaneous bacteria Summary The skin is the largest organ at the interface between environment and host. It plays a major protective role against pathogens as physical barrier, as site of first recognition, and as orchestrator of consecutive immune responses. In this process, immunological crosstalk between skin-resident and immune cells is required, and fixed innate im- mune responses were previously believed to orchestrate adaptive immunity of B and T lymphocytes. Today, we understand that diverse qualities of immune responses to different microbes need to be regulated by also varying responses at the level of first microbe recognition through receptors of the innate immune system. Only fine-tun- ing of the innate immune system allows for the orchestration of immune responses to the microbiota in the absence of inflammation as well as to pathogens in the context of protective responses including inflammation. Understanding how innate immunity precisely adapts is also important for diseases such as atopic dermatitis (AD) with chro- nic inflammation. In this review, we present data on how the innate immune system actually fine-tunes its responses with special focus on the immunological consequen- ces of cutaneous innate immune sensing through TLR2. These new insights are highly relevant for understanding microbiota-associated state of health, immune defense, and the pathogenesis underlying chronic cutaneous inflammation as seen in AD. Yuliya Skabytska 1,2 , Susanne Kaesler 1,2 , Thomas Volz 1 , Tilo Biedermann 1 (1) Department of Dermatology and Allergology, TUM School of Medicine, Technische Universität München, Germany (2) Department of Dermatology, Eberhard-Karls-University Tübingen, Germany Pathogen-associated molecular patterns and pattern recognition receptors Pattern recognition receptors (PRRs) recognize highly con- served molecular patterns, known as pathogen-associated molecular patterns (PAMPs). Pathogen-associated molecular patterns are substances from bacteria, fungi, or protozoa. These innate responses occur rapidly, and are efficient in killing pathogens, thereby limiting pathogen-induced tissue injury. There are several classes of PRRs: Toll-like receptors (TLRs), NOD-like receptors (NLRs), RIG-I-like receptors (RLRs), and C-type lectin receptors (CLRs). Among PRRs, TLRs are a well characterized family with distinct recogniti- on profiles [1]. TLR2 and its coreceptors TLR1 and TLR6 are especially important in response to Gram-positive bacteria. TLR2 is expressed both on innate (DCs, macrophages) and adaptive immune cells (T and B cells) as well as on nonimmu- ne cells (keratinocytes) [2–4]. TLR2 heterodimers and ligands and their role in cutaneous inflammation When compared to most other TLRs, TLR2 recognizes a remarkably broad range of PAMPs. These include, among others, bacterial lipopeptides (Lpp) from Gram-positive bac- teria. This high diversity of ligand recognition by TLR2 is in part facilitated by its unique ability to homodimerize as well as heterodimerize with TLR1 and TLR6. TLR1 is re- quired for the recognition of bacterial triacylated lipopro- teins [5]. Diacylated components interact with TLR2/TLR6