**About the Editors**

#### **Silvia Fischer**

Silvia Fischer received her doctor's degree at the Institute of Biochemistry of the Justus-Liebig-University in Giessen. After her post-doc time in Los Angeles, where she studied the generation and application of liposomes, she studied regulatory mechanisms and specific properties of the endothelium, especially the regulation of the permeability of the blood-brain barrier as well as processes of angiogenesis at the Max-Planck-Institute in Bad Nauheim. Since several years she investigated the role of extracellular RNA as danger associated molecular pattern in inflammatory processes and diseases at the Institute of Biochemistry in Giessen. She could demonstrate that extracellular RNA contributes to inflammatory pathologies such as stroke, myocardial infarction, rheumatoid arthritis, or cancer growth.

#### **Elisabeth Deindl**

Elisabeth Deindl (Dr) received her doctor's degree at the ZMBH in Heidelberg, Germany, where she worked on hepatitis B viruses. Thereafter, she joined the lab of Wolfgang Schaper at the Max-Planck-Institute in Bad Nauheim, where she started to decipher the molecular mechanisms of arteriogenesis. After a short detour on stem cells, she focused again on arteriogenesis becoming a leading expert in the field. By using a peripheral model of arteriogenesis, she demonstrated that collateral artery growth is a matter of innate immunity and presents a blueprint of sterile inflammation, which is locally triggered by extracellular RNA.

### *Editorial* **State of the Art of Innate Immunity—An Overview**

**Silvia Fischer 1,\* and Elisabeth Deindl 2,3**

	- <sup>3</sup> Biomedical Center, Institute of Cardiovascular Physiology and Pathophysiology, Ludwig-Maximilians-University, Planegg-Martinsried, 82152 Munich, Germany
	- **\*** Correspondence: silvia.fischer@biochemie.med.uni-giessen.de; Tel.: +49-641-9947440

The innate immune system is the first line of defense against bacterial and viral infections and sterile inflammation through the recognition of pathogen-associated molecular patterns (PAMPs) as well as danger-associated molecular patterns (DAMPs) by pathogenrecognition receptors (PRRs), and produces proinflammatory and antiviral cytokines and chemokines [1].

This Special Issue of *Cells* is devoted to many aspects of innate immunity and gives an overview of different DAMPs, immune cells, special mechanisms, and therapeutic options for treating diseases related to chronic inflammation or infections.

One of the well-known DAMPs is the high-mobility group box 1 protein (HMGB1), which is either passively released by dying cells or actively secreted by immune and other cells and was described as implicated in both stimulating and inhibiting innate immunity. Andersson et al. reported that the pro- and anti-inflammatory activities of HMGB1 depend on post-translational modification of its disulfide bonds by binding to different extracellular cell surface receptors either directly or as a cofactor of PAMPs [2].

Another DAMP, extracellular ribosomal RNA, which is released under pathological conditions from damaged tissue, acts synergistically with Toll-like receptor 2 ligands, inducing the release of cytokines in a nuclear factor kappa B-dependent manner in vitro as well as in vivo. Grote et al. suggest that extracellular RNA might sensitize Toll-like receptor 2 to enhance the immune response under pathological conditions and therefore might serve as a new target for the treatment of bacterial or viral infections [3].

Arnholdt et al. demonstrate that cells related to innate immunity and influencing immunoregulatory and inflammatory processes, such as gamma delta T cells, play an important role in angiogenesis and tissue generation. By using a femoral artery ligation model in mice, depletion of this subset of T cells was demonstrated to impair angiogenesis, increase the number of leukocytes and inflammatory M1-like macrophages, and promote the formation of neutrophil extracellular traps (NETs) [4].

The topic of autoinflammation is also covered in this Special Issue. The review of P. Georgel provides some examples of autoimmune/autoinflammatory diseases caused by the deregulated expression of type I interferons and interleukin-1β. The role of interleukin-1 and type I interferons and their crosstalk in autoinflammatory diseases such as rheumatic diseases are analyzed to reveal novel therapeutic opportunities [5].

Gullet et al. discuss the key components of programmed cell death pathways and highlight the plasticity of pyroptosis, apoptosis, and necroptosis as well as significant crosstalk among these pathways. The concept of PANoptosis, an inflammatory cell death pathway that integrates components of different cell death pathways and is implicated in driving innate immune responses and inflammation, is explained [6].

A review by Papendorf et al. provides a comprehensive overview of molecular pathogenesis disorders caused by proteostasis perturbations, and current knowledge of

**Citation:** Fischer, S.; Deindl, E. State of the Art of Innate Immunity—An Overview. *Cells* **2022**, *11*, 2705. https://doi.org/10.3390/ cells11172705

Received: 24 August 2022 Accepted: 26 August 2022 Published: 30 August 2022

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**Copyright:** © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

the various mechanisms by which impaired proteostasis promotes autoinflammation is summarized [7].

To investigate the crosstalk between coagulation and innate immunity, the effect of thrombin on macrophage polarization is investigated by Ukan et al. Results demonstrate that thrombin induces an anti-inflammatory phenotype in macrophages, which shows similarities to as well as differences from the classical M2 polarization states regarding the expression of secreted modular Ca2+-binding protein [8].

To investigate insect innate immunity, the in vitro cultivation of primary hemocytes from *D. Suzuki* third-instar larvae is described by Carrau et al. as a valuable tool for investigating hemocyte-derived effector mechanisms against pathogens, particularly for the formation of extracellular traps [9].

Drugs such as ganciclovir and its pro-drug valganciclovir are often used to treat viremic patients transfected with, e.g., human cytomegalovirus (HCMV). Results from Landázuri now suggest that binding and signaling through endothelin receptor B (ETBR) is crucial for viral replication and that selected ETBR blockers inhibit HCMV infections [10].

Lin et al. report that albumin attenuates chronic liver diseases (CLDs) via alleviating inflammation of Kupffer cells caused by bacterial products, which might provide a compelling rationale for albumin therapy in patients with CLDs [11].

**Funding:** This research received no external funding.

**Conflicts of Interest:** The authors declare no conflict of interest.

#### **References**

