Mechanisms of Innate Immune Activation and Regulation in Health and Disease (Volume 2)

Dear Colleagues, 

This Special Issue follows the publication of the first volume on “Mechanisms of Innate Immune Activation and Regulation in Health and Disease”, which presented more than 10 interesting papers.

Besides representing the first line of defense against invading pathogens, innate immunity also instructs adaptive effectors to mount appropriate, pathogen-tailored responses. Excessive or unwanted activation of innate cells may thus harm the organisms by fostering autoimmunity, non-resolving inflammation, or both. On these premises, understanding the mechanisms of innate immune activation is of pivotal importance to identify new therapeutic targets and strategies to cope with hyperinflammation.

Innate immune cells get activated upon recognition of structural features of classes of pathogens (pathogen-associated molecular patterns, PAMPs) by specific sensors named pattern recognition receptors (PRRs). In addition to PAMPs, PRRs also recognize self-danger signals (damage-associated molecular patterns, DAMPs) that initiate non-infectious (sterile) inflammatory responses. Because of the intrinsic nature of DAMPs, sterile inflammation is a potentially self-renewing phenomenon.

The importance of DAMPs and gain-of-function mutations of PRRs as triggers of autoinflammatory and autoimmune diseases is a prevailing topic of research and discovery. The roles of cytoplasmic DNA in the pathogenesis of Aicardi-Goutières syndrome type I, of the gain-of-function mutation of IFIH1 in Aicardi-Goutières syndrome type 7 and of accumulating self-nucleic acids in complex, multifactorial diseases such as Systemic Lupus Erithematosus and psoriasis are only mere examples of a vivid field of investigation.  On the other hand, autoimmune and autoinflammatory manifestations recently observed in the context of the coronavirus disease 2019 (COVID-19) pandemic, such as paediatric inflammatory multisystemic syndrome (PIMS), have potently reaffirmed the strong relationship between PAMPs, non-sterile inflammation and the unleashing of uncontrolled immune responses.

This Special Issue aims to gather original research and review articles dealing with any aspect of controlled or uncontrolled innate immune activation, with a special focus on new molecular targets and therapies to control non-resolving inflammation. Suggested topics:

1. Identification and characterization of novel PAMPs and DAMPs
2. PRR mutations and dysregulation of the immune response
3. Mechanisms of infectious and sterile innate immune activation
4. Mechanisms fuelling non-resolving inflammation
5. Mechanisms of inflammation-dependent tissue damage
6. Anti-inflammatory properties of old and new drugs
7. Novel targets for old and new drugs to control hyperinflammation
8. DAMPs as diagnostic and prognostic biomarkers

Pure clinical/investigation studies cannot be considered, but clinical submissions with biomolecular experiments are welcomed. 

Dr. Daniela Bosisio
Dr. Valentina Salvi
Guest Editors

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