In this issue: Fine tuners of immunity and their role in infectious and non-infectious diseases

Immune responses are the result of complex biochemical signaling events aimed to lead to elimination of pathogens and other undesirable molecular and cellular threats developed within the host as a consequence of tissue injuries. To optimize responses to the nature of the immunological threats and minimize errors in biochemical information flow during cell signaling, immune cells evolved a variety of molecular switches and networks. The majority of molecular switches act at post-transcriptional and post-translational levels, to establish appropriate type, intensity and duration of immune responses. Suboptimal functioning of this cell signaling network may lead to immunopathology. Hence the focus of this issue of the International Reviews of Immunology is to showcase the role of modulating switches in infectious and autoimmune diseases (Fig. 1).

Perturbation of host homeostasis as consequence of infection or other tissue damage, leads to tissue stress and cell damage, with subsequent release of intracellular contents comprising danger- or damage-associated molecular patterns (DAMPs), in the extracellular environment. These cellular materials may induce different degree of inflammation and without appropriate process resolution, facilitate the development of autoimmune disease. In the first review article of this issue, Alvarez et al. highlighted the potentially devastating effects of sterile inflammation, initiated upon sensing of various endogenous molecules by an array of immune sensors, leading to autoimmune diseases. The authors discussed the underlining molecular mechanisms of DAMPs sensing, leading to immune signaling and synthesis of inflammatory cytokines. The article also discusses potential therapeutic targets for controlling inflammation and autoimmunity in particular.

Mycobacterium tuberculosis is still a global problem, causing 1.8 million deaths worldwide. This death toll is further enhanced by the emergence of multiple drug-resistant strains of M. tuberculosis. Discovery of new immune defense mechanisms and immune regulating pathways enhanced the fundamental knowledge of M. tuberculosis pathogenesis. Thus it is important to revisit the host-M. tuberculosis interaction under the light of these new discoveries, to more effectively target this pathogen. The second review article by Khan et al., highlights the role of autophagy in the elimination of M. tuberculosis without enhancing inflammation, thereby minimizing or avoiding altogether immunopathology. The article advances the concept of utilizing modulators for cellular autophagy as a general strategy to combat M. tuberculosis infection and the associated immunopathology (Fig. 1).

Figure 1. Role of immune regulators in infectious and non-infectious disease. Mbact, Mycobacteria and Treg, regulatory T cells.

A category of non-coding short RNAs also known as micro(mi)RNAs, are potent post-transcriptional regulators of gene expression through influencing messenger RNAs. The expression of genes is regulated by miRNA binding to 3′-untranslated regions (UTR) of the transcript, to control a wide-range of biological processes including host defense. The third review article in this issue, by Keck et al., describes the crucial role of miRNA in regulating various aspects of innate and adaptive immunity such as ontogeny, and the functional aspects of different immune cells during microbial infection. The review also focuses on how miRNAs direct the immune responses during gram-negative bacterial infection (Fig. 1).

The last review article of this issue by Zhan et al. discusses the regulatory role of E3 ubiquitin ligase known as Carboxyl terminal of Hsp70-interacting protein (CHIP) in innate and adaptive immunity. This pathway is primarily involved with protein disposal mechanisms in the cell, and is intimately connected to the cell stress mechanisms. The article also discusses the effects of dysregulation of CHIP on immune-associated diseases.