Towards a Holistic Model of Care for Moral Injury: An Australian and New Zealand Investigation into the Role of Police Chaplains in Supporting Police Members following exposure to Moral Transgression.

Police members can be exposed to morally transgressive events with potential for lasting psychosocial and spiritual harm. Through interviews with police members and police chaplains across Australia and New Zealand, this qualitative study explores the current role that police chaplains play in supporting members exposed to morally transgressive events. The availability of chaplains across police services and the close alignment between the support they offer, and the support sought by police, indicates they have an important role. However, a holistic approach should also consider organizational factors, the role of leaders, and access to evidence-based treatment in collaboration with mental health practitioners.

STING, nanoparticles, autoimmune disease and cancer: a novel paradigm for immunotherapy?

DNA has potent immunogenic properties that are useful to enhance vaccine efficacy. DNA also incites hyperinflammation and autoimmunity if DNA sensing is not regulated. Paradoxically, DNA regulates immunity and autoimmunity when administered systemically as DNA nanoparticles. DNA nanoparticles regulated immunity via cytosolic DNA sensors that activate the signaling adaptor stimulator of interferon genes. In this review, we describe how DNA sensing to activate stimulator of interferon genes promotes regulatory responses and discuss the biological and clinical implications of these responses for understanding disease progression and designing better therapies for patients with chronic inflammatory diseases, such as autoimmune syndromes or cancer.

Cytosolic DNA sensing via the stimulator of interferon genes adaptor: Yin and Yang of immune responses to DNA.

DNA is immunogenic and many cells express cytosolic DNA sensors that activate the stimulator of interferon genes (STING) adaptor to trigger interferon type I (IFN-ß) release, a potent immune activator. DNA sensing to induce IFN-ß triggers host immunity to pathogens but constitutive DNA sensing can induce sustained IFN-ß release that incites autoimmunity. Here, we focus on cytosolic DNA sensing via the STING/IFN-ß pathway that regulates immune responses. Recent studies reveal that cytosolic DNA sensing via the STING/IFN-ß pathway induces indoleamine 2,3 dioxygenase (IDO), which catabolizes tryptophan to suppress effector and helper T-cell responses and activate Foxp3-lineage CD4(+) regulatory T (Treg) cells. During homeostasis, and in some inflammatory settings, specialized innate immune cells in the spleen and lymph nodes may ingest and sense cytosolic DNA to reinforce tolerance that prevents autoimmunity. However, malignancies and pathogens may exploit DNA-induced regulatory responses to suppress natural and vaccine-induced immunity to malignant and infected cells. In this review, we discuss the biologic significance of regulatory responses to DNA and novel approaches to exploit DNA-induced immune responses for therapeutic benefit. The ability of DNA to drive tolerogenic or immunogenic responses highlights the need to evaluate immune responses to DNA in physiologic settings relevant to disease progression or therapy.

Altered tryptophan metabolism as a paradigm for good and bad aspects of immune privilege in chronic inflammatory diseases.

The term "immune privilege" was coined to describe weak immunogenicity (hypo-immunity) that manifests in some transplant settings. We extended this concept to encompass hypo-immunity that manifests at local sites of inflammation relevant to clinical diseases. Here, we focus on emerging evidence that enhanced tryptophan catabolism is a key metabolic process that promotes and sustains induced immune privilege, and discuss the implications for exploiting this knowledge to improve treatments for hypo-immune and hyper-immune syndromes using strategies to manipulate tryptophan metabolism.