Neuroinflammatory and neurodegenerative diseases are a major public health problem worldwide, especially with the increase of life-expectancy observed during the last decades. For many of these diseases, we still lack a full understanding of their etiology and pathophysiology. Nonetheless their association with mitochondrial dysfunction highlights this organelle as an important player during CNS homeostasis and disease. Markers of Parkinson (PD) and Alzheimer (AD) diseases are able to induce innate immune pathways induced by alterations in mitochondrial Ca2+ homeostasis leading to neuroinflammation. Additionally, exacerbated type I IFN responses triggered by mitochondrial DNA (mtDNA), failures in mitophagy, ER-mitochondria communication and mtROS production promote neurodegeneration. On the other hand, regulation of mitochondrial dynamics is essential for CNS health maintenance and leading to the induction of IL-10 and reduction of TNF-α secretion, increased cell viability and diminished cell injury in addition to reduced oxidative stress. Thus, although previously solely seen as power suppliers to organelles and molecular processes, it is now well established that mitochondria have many other important roles, including during immune responses. Here, we discuss the importance of these mitochondrial dynamics during neuroinflammation, and how they correlate either with the amelioration or worsening of CNS disease.

Information available to the public influences the approach of the population toward vaccination against influenza compared with other preventative approaches. In this study, we have analyzed the first 200 websites returned by searching Google on two topics (prevention of influenza and influenza vaccine), in English and Italian. For all the four searches above, websites were classified according to their typology (government, commercial, professional, portals, etc.) and for their trustworthiness as defined by the Journal of the American Medical Association (JAMA) score, which assesses whether they provide some basic elements of information quality (IQ): authorship, currency, disclosure, and references. The type of information described was also assessed to add another dimension of IQ. Websites on influenza prevention were classified according to the type of preventative approach mentioned (vaccine, lifestyle, hygiene, complementary medicine, etc.), whether the approaches were in agreement with evidence-based medicine (EBM) or not. Websites on influenza vaccination were classified as pro- or anti-vaccine, or neutral. The great majority of websites described EBM approaches to influenza prevention and had a pro-vaccine orientation. Government websites mainly pointed at EBM preventative approaches and had a pro-vaccine orientation, while there was a higher proportion of commercial websites among those which promote non-EBM approaches. Although the JAMA score was lower in commercial websites, it did not correlate with the preventative approaches suggested or the orientation toward vaccines. For each of the four search engine result pages (SERP), only one website displayed the health-of-the-net (HON) seal. In the SERP on vaccines, journalistic websites were the most abundant category and ranked higher than average in both languages. Analysis using natural language processing showed that journalistic websites were mostly reporting news about two specific topics (different in the two languages). While the ranking by Google favors EBM approaches and, in English, does not promote commercial websites, in both languages it gives a great advantage to news. Thus, the type of news published during the influenza season probably has a key importance in orienting the public opinion due to its high visibility. This raises important questions on the relationships between health IQ, trustworthiness, and newsworthiness.

HLA mismatching is an important risk factor for antibody-mediated rejection and transplant failure. With the realization HLA antibodies recognize epitopes rather than antigens, it has become apparent that donor-recipient compatibility should be assessed at the epitope level. Recent developments have increased our understanding of the structural basis of HLA antigenicity, i.e., the reactivity with specific antibody and, immunogenicity, i.e., the ability to induce an antibody response. HLAMatchmaker is a computer algorithm that considers each HLA antigen as a series of small configurations of polymorphic residues referred to as eplets as essential components of HLA epitopes. This article addresses the relevance of determining epitope-specificities of HLA antibodies in the identification of acceptable mismatches for sensitized patients considered for transplantation. Permissible mismatching for non-sensitized patients aimed to prevent or reduce HLA antibody responses could consider epitope loads of mismatched antigens and the recently developed non-self-self paradigm of epitope immunogenicity.

Single trauma injuries or isolated fractures are often manageable and generally heal without complications. In contrast, high-energy trauma results in multi/poly-trauma injury patterns presenting imbalanced pro- and anti- inflammatory responses often leading to immune dysfunction. These injuries often exhibit delayed healing, leading to fibrosis of injury sites and delayed healing of fractures depending on the intensity of the compounding traumas. Immune dysfunction is accompanied by a temporal shift in the innate and adaptive immune cells distribution, triggered by the overwhelming release of an arsenal of inflammatory mediators such as complements, cytokines and damage associated molecular patterns (DAMPs) from necrotic cells. Recent studies have implicated this dysregulated inflammation in the poor prognosis of polytraumatic injuries, however, interventions focusing on immunomodulating inflammatory cellular composition and activation, if administered incorrectly, can result in immune suppression and unintended outcomes. Immunomodulation therapy is promising but should be conducted with consideration for the spatial and temporal distribution of the immune cells during impaired healing. This review describes the current state of knowledge in the spatiotemporal distribution patterns of immune cells at various stages during musculoskeletal wound healing, with a focus on recent advances in the field of Osteoimmunology, a study of the interface between the immune and skeletal systems, in long bone fractures. The goals of this review are to (1) discuss wound and fracture healing processes of normal and delayed healing in skeletal muscles and long bones; (2) provide a balanced perspective on temporal distributions of immune cells and skeletal cells during healing; and (3) highlight recent therapeutic interventions used to improve fracture healing. This review is intended to promote an understanding of the importance of inflammation during normal and delayed wound and fracture healing. Knowledge gained will be instrumental in developing novel immunomodulatory approaches for impaired healing.

Events related to HCMV infection drive accumulation of functionally enhanced CD57posNKG2Cpos adapted NK cells. We investigated NK cell adaptation to HCMV along a proposed continuum progressing from acute activation through maturation and memory formation towards functional exhaustion. Acute exposure to conditioned medium collected 24 h after HCMV infection (HCMVsn) increased NK cell cytotoxicity for all HCMV-seronegative and seropositive donors tested, with mean 38 and 29% boosts in natural and antibody-dependent cell-mediated cytotoxicity (ADCC), respectively. Increases in NK cell cytotoxicity were completely abrogated by blocking type I interferon (IFN) receptors and equivalent responses occurred with exposure to IFN-α2 alone at the same concentration present in HCMVsn. To study longer term effects of HCMV infection, we focused on three groups of human immunodeficiency virus (HIV)-infected subjects distinguished as HCMV-seronegative or HCMV-seropositive with either high (>20%) or low (<6%) fractions of their NK cells expressing NKG2C. The NK cells of all three HIV-infected groups responded to HCMVsn and IFN-α2 in a manner similar to the NK cells of either HCMV-seronegative or seropositive controls. Neither HCMV status, nor the extent of phenotypic evidence of adaptation to HCMV infection significantly affected mean levels of ADCC or CD16-mediated NK cell degranulation and IFN-γ production compared between the HIV-infected groups. Levels of IFN-γ production correlated significantly with the fraction of NK cells lacking FcεRIγ (FcRγ), but not with the fraction of NK cells expressing NKG2C. There was negligible expression of exhaustion markers Lag-3 and PD-1 on NK cells in any of the groups and no significant difference between groups in the fraction of NK cells expressing Tim-3. The fraction of NK cells expressing Tim-3 was unaffected by CD16 stimulation. Relative to the total NK cell population, responses of Tim-3-expressing cells to CD16 stimulation were variably compromised in HCMV seronegative and seropositive groups. In general, NK cell function in response to signaling through CD16 was well preserved in HIV infection and although HCMV had a clear effect on NK cell FcRγ and NKG2C expression, there was little evidence that the level of adaptation to HCMV infection affected CD16-dependent NK cell signaling in HIV infection.