Immune system pathogenesis is prevented by the neutralization of the systemictrans-sialidase fromTrypanosoma cruziduring severe infections

Current concept in periodontal diseases (PDs) states that it is the host's response toward the periodontal pathogens which leads to tissue destruction and attachment loss. Hence the role of immune response in the progression and resolution of PD must be considered vital. Any alteration in the immune system disturbs the homeostasis of the periodontium. Decline in immune system is the hallmark of aging, leading to increased susceptibility of elderly individuals to bacterial infections. The periodontal apparatus which is being constantly exposed to plaque biofilm is more vulnerable to destruction in aged individuals. Ageing related alterations in immune system has been discussed elsewhere as a contributor to various chronic inflammatory diseases like atherosclerosis, preterm, and low birth weight, etc. This paper reviews on the possible role of aging in periodontal destruction through altered immunity. Aging has long been associated with altered systemic inflammation. It has been discussed whether (1) this systemic inflammation is a consequence of increased occurrence of chronic inflammatory diseases upon aging or (2) aging associated systemic inflammation leads to such diseases. The immune responses which are protective at the first stages of life might result detrimental in the elderly. Hence it might be very difficult to individuate genetic profiles that might allow to identify individuals with a major risk for one or more age related diseases. Taking this into consideration, the cause of PDs in elderly is addressed with a systemic approach in order to understand the complex interplay between the aging immunity and PDs.

Alterations in composition of immune cells and impairment of anti-tumor immune response in aged oral cancer-bearing mice

Exercise-induce hyperalgesia, complement system and elastase activation in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome - a secondary analysis of experimental comparative studies.

Recently, increasing research stressed the presence of subthreshold autistic traits in patients with other psychiatric conditions. In this framework, a significant relationship between anorexia nervosa (AN) and the autism spectrum has been frequently reported, in particular among female samples, to the point that AN has been hypothesized to be a female phenotype of autism spectrum disorder (ASD). On the other hand, among subjects with ASD has been reported a higher prevalence of immune diseases and altered immune functions. While these reports seem to support an association between neurodevelopmental and immune system alterations in ASD, the relationship between the immune system and the broader autism spectrum, including its subthreshold manifestations, remains poorly investigated. In this report, we described the presence of autistic traits in a male inpatient with AN and separation anxiety disorder, who also show a diagnosis of Behçet's syndrome (BS). This case seems to further stress the association between AN and the autism spectrum, which may not be limited to the female gender. Moreover, it further suggests a deeper link between neurodevelopmental and immune system alterations. Implications are discussed in light of the more recent neurobiological and psychopathological hypothesis about the autism spectrum.

Trypanosoma cruzi, the agent of the American trypanosomiasis or Chagas disease, bypasses its lack of de novo synthesis of sialic acids by expressing a surface-anchored trans-sialidase. This enzyme transfers sialic acid residues from the host's sialylglycoconjugates to the parasite's galactosylglycoconjugates. In addition to carrying out a pivotal role in parasite persistence/replication within the infected mammal, the trans-sialidase is shed into the bloodstream and induces alterations in the host immune system by modifying the sialylation of the immune cells. A major obstacle to understand these events is the difficulty to identify the transferred sialic acid among all those naturally occurring on the cell surface. Here, we report the use of azido-modified unnatural sialic acid to identify those molecules that act as cell surface acceptors of the sialyl residue in the trans-sialidase-catalyzed reaction, which might then be involved in the immune alterations induced. In living parasites, we readily observed the transfer of azido-sialic acid to surface mucins. When evaluating mouse thymocytes and splenocytes as acceptors of the azido-sugar, a complex pattern of efficiently tagged glycoproteins was revealed. In both leukocyte populations, the main proteins labeled were identified as different CD45 isoforms. Disruption of the cell architecture increased the number and the molecular weight distribution of azido-sialic acid tagged proteins. Nevertheless, CD45 remained to be the main acceptor. Mass spectrometry assays allowed us to identify other acceptors, mainly integrins. The findings reported here provide a molecular basis to understand the abnormalities induced in the immune system by the trans-sialidase during T. cruzi infection.

Amyotrophic lateral sclerosis is a disease of which the underlying cause and pathogenesis are unknown. Cumulatative data clearly indicates an active participation by the immune system in the disease. An increasingly recognized theory suggests a non-cell autonomous mechanism, meaning that multiple cells working together are necessary for the pathogenesis of the disease. Observed immune system alterations could indicate an active participation in this mechanism. Damaged motor neurons are able to activate microglia, astrocytes and the complement system, which further can influence each other and contribute to neurodegeneration. Infiltrating peripheral immune cells appears to correlate with disease progression, but their significance and composition is unclear. The deleterious effects of this collaborating system of cells appear to outweigh the protective aspects, and revealing this interplay might give more insight into the disease. Markers from the classical complement pathway are elevated where its initiator C1q appears to derive primarily from motor neurons. Activated microglia and astrocytes are found in close proximity to dying motor neurons. Their activation status and proliferation seemingly increases with disease progression. Infiltrating monocytes, macrophages and T cells are associated with these areas, although with mixed reports regarding T cell composition. This literature review will provide evidence supporting the immune system as an important part of ALS disease mechanism and present a hypothesis to direct the way for further studies.

Inflammation and Immune System Alterations in Frailty

Deciphering the intricacies of immune system dysfunction and its impact on diabetes mellitus: Revisiting the communication strategies to manage diabetes mellitus

The role of the immune system in psychiatric disorders has been garnering increased attention (1). In the absence of established classic immune-mediated neuropathology such as that seen in autoimmune or infectious disorders, the interpretations of these findings have evoked considerable controversy and debate. Previously, members of the Lewis teamattheUniversityofPittsburghreportedimmunesystem activation including higher mRNA levels of interferoninduced transmembrane protein (IFITM) in the dorsolateral prefrontal cortex from schizophrenia cases (2). In their follow-up studyin thisissue,Volketal.(3) explore a basis for this increased gene expression and seek to evaluate whether a prenatal immune-related insult, as opposed to a postnatal exposure to infectious agents, causes the observed immune gene expression increase in the prefrontal cortex of adults diagnosed with schizophrenia. The authors identify several genes that are significantly overexpressed in dorsolateral prefrontal cortex gray matter ofschizophreniasubjectsincomparisontomatchedcontrols. Specifically, they report significant increases in mRNA levels for interleukin-6 (IL-6) and interferon-b, both of which induce the expression of IFITM. Interestingly, Schnurri-2 mRNA is significantly lowered, which decreases IFITM levels by inhibiting NF-kB, a well-known transcription regulator of the immune gene network. The authors’ findings collectively amount to a significant increase in IFITM in dorsolateral prefrontal cortex gray matter of subjects diagnosed with schizophrenia. Of note, it is well known that IFITM and other immune genes reported here constitute an immune response to a host of viral infections, including influenza A, dengue, and West Nile virus (4). This raises questions as to the clinical, etiological, and/or functional relevance of IFITM expression in schizophrenia. The increasedexpressionofinterferon-bandNF-kBmakesmatters more complicated, since these are master regulators of many genes. One of the basic functions of components of the immune system is to protect the host against pathogens. However, they may also play a separate role distinct from immunologicalresponses.Ofparticularinterestisareporton

Simple SummaryA common characteristic of multiple myeloma (MM) is the dysfunction of patients’ immune system, a condition termed immunosuppression. This state is mainly due to alterations in the number and functionality of the principal immune populations. In this setting, immunotherapy has acquired high relevance in the last years and the investigation of agents that boost the immune system represent a field of interest. In the present review, we will summarize the main cellular and molecular alterations observed in MM patients’ immune system. Furthermore, we will describe the mechanisms of action of the four immunotherapeutic drugs approved so far for the treatment of MM, which are part of the group of monoclonal antibodies (mAbs). Finally, the immune-stimulating effects of several therapeutic agents are described due to their potential role in reversing immunosuppression and, therefore, in favoring the efficacy of immunotherapy drugs, such as mAbs, as part of future pharmacological combinations.Immunosuppression is a common feature of multiple myeloma (MM) patients and has been associated with disease evolution from its precursor stages. MM cells promote immunosuppressive effects due to both the secretion of soluble factors, which inhibit the function of immune effector cells, and the recruitment of immunosuppressive populations. Alterations in the expression of surface molecules are also responsible for immunosuppression. In this scenario, immunotherapy, as is the case of immunotherapeutic monoclonal antibodies (mAbs), aims to boost the immune system against tumor cells. In fact, mAbs exert part of their cytotoxic effects through different cellular and soluble immune components and, therefore, patients’ immunosuppressive status could reduce their efficacy. Here, we will expose the alterations observed in symptomatic MM, as compared to its precursor stages and healthy subjects, in the main immune populations, especially the inhibition of effector cells and the activation of immunosuppressive populations. Additionally, we will revise the mechanisms responsible for all these alterations, including the interplay between MM cells and immune cells and the interactions among immune cells themselves. We will also summarize the main mechanisms of action of the four mAbs approved so far for the treatment of MM. Finally, we will discuss the potential immune-stimulating effects of non-immunotherapeutic drugs, which could enhance the efficacy of immunotherapeutic treatments.

Prediction of Early Death and Severe Infections during Novel Agent-Based Induction Therapy in Newly-Diagnosed Multiple Myeloma: An Intergroup Analysis from the German Speaking Myeloma Multicenter Group, the Dutch-Belgian Cooperative Trial Group for Hematology Oncology Foundation and the European Myeloma Network

The present thesis deals with the interface of the immune system, ADHD and the influence of ADHD medication on the proteins of the immune system. The immune system is increasingly discussed as a possible confounder of many pathomechanisms. This is particularly the case in psychiatric diseases and thus the subject of current research in diseases such as Major Depressive Disorder and Schizophrenia. Also, in ADHD, an involvement of cells and mediators of the immune system is suspected, and several studies with child populations have already presented strong evidence. ADHD is notably a mental disorder that not only affects children but also presents a burden in adulthood. Nevertheless, research on this proportion of affected individuals has recently been neglected, and statements about immune system involvement cannot be fundamentally transferred from children to adults. Ultimately, unstable hormones seriously influence the release of immune cells, so children and adolescents are most likely not suitable to assess an immune system alteration in ADHD universally. Another aspect that may influence the release of immune cells is the use of ADHD medication, which significantly models the Dopamine (DA) household. This modulation is thought to improve symptoms, especially in individuals severely affected by ADHD. DA is a neurotransmitter of the central nervous system and, simultaneously, one of the most relevant immune modulators in the body’s periphery. The so-called neuroimmune crosstalk characterizes the mutual influence of immune cells and neurotransmitters such as DA. Therefore, an imbalance of the immune system cells could contribute to an imbalance in DA transmission, and vice versa: a disturbed DA transmission could provoke a disturbed release of immune cells. Accordingly, balance in one of the systems could hypothetically contribute to balance in the other. Consequently, this work aims to discover to what extent ADHD in adults is a disease associated with an altered immune system, how ADHD medication affects this relationship and what other factors, such as symptom severity or increased stress, are contributing to inflammation in ADHD. A Systematic Review and Meta-Analysis of published research present the first outcome of this thesis. Heterogeneous study designs, methodology, and results characterize the Systematic Review result. Thus, a conclusion can only be drawn incompletely, suggesting that the frequently studied IL-6 is associated with increased protein levels in participants with ADHD. Based on six studies with child ADHD participants and healthy controls, the Meta-Analysis investigated four inflammatory proteins (IL-1α, IL-6, IL-10, TNF-α) and found IL-6 significantly increased (SMD = 0.75, 95%CI: 0.02, 1,48; p-value = 0.043) and TNF-α (SMD = -0.30, 95%CI: -0.53, -0.06; p-value = 0.013) to be significantly decreased in ADHD compared to healthy controls. For the proteomics analysis, 72 protein levels of 126 ADHD participants from the “PROBIA” study and nine “Healthy Controls” from the “MODULATE” study were examined. An initial analysis revealed 22 proteins significantly different between ADHD participants and “Healthy Controls”. A discovery and validation dataset approach confirmed five proteins (CD6, CD5, CASP-8, CX3CL1 and Sulfotrans-ferase1A1 (ST1A1), p-value ≤ 0.038). There was no difference in inflammatory protein levels regarding ADHD medication status (p.adj ≥ 0.282) and type (p.adj ≥ 0.807). Furthermore, an unsupervised cluster analysis was used to explore which characteristics could be associated with the increased inflammatory protein levels in the overall ADHD group. Regardless of medication status, the cluster analysis found a specific cluster, primarily containing “pro-inflammatory” proteins of the NF-kB signaling pathway, that was significantly different between two ADHD subgroups (higher (HIP) and lower inflammatory potential (LIP), Pil-lai's Trace Test = 0.87, F = 29.64, p-value < 0.001; post-hoc ANOVA: p-value < 0.001, p.adj < 0.001). The HIP subgroup was consequently associated with increased stress (p-value < 0.001), higher suicidality risk (p-value = 0.032) and higher CGI scoring (p-value = 0.030). Ultimately, Systematic Review, Meta-Analysis, and experimental proteomic analysis results suggest that ADHD in childhood and adulthood might be associated with altered inflammatory proteins, especially in a subgroup of affected individuals with the above-described characteristics. The present work aimed to examine a large number of inflammatory proteins in an adult ADHD population while also investigating the effect of ADHD medication on specific proteins. No influential role was found, suggesting that ADHD medication does not cause inflammation, in contrast to what is suggested by animal studies. In future settings, efforts could be directed towards enhancing “anti-inflammatory” interventions, such as stress reduction techniques, nutritional interventions, and resilience training, particularly in sub-groups affected by ADHD, complementing ADHD medication strategies.

Following the pandemic in 2020, physical health has generally declined. All of this is brought on by modifications to the body's immune system and the consequences of sequelae. The current research gap is caused by the neglect of COVID-19's after effects. In this paper, the relationship between immune system changes, complications and their physical conditions was studied, and preliminary results on the harm and prevention of the sequelae were obtained. The immune system's alterations during the epidemic infection and its consequences are the main topics of this article, including cytokine storms, inflammatory responses, and changes in immune cells. At the same time, the article explores the relationship between complications and underlying health conditions, such as chronic diseases and autoimmune diseases, and the harm they cause. Through observation and analysis in the later stages of the epidemic, the article explores the reasons for the general decline in people's physical fitness and changes in the immune system. In the future, it is hoped that there will be improvements in disease analysis and prevention measures after pandemic diseases.

Comparative transcriptomics of whole blood can be used to evaluate the systemic host response and its concordance between human and mouse malaria and aid the selection of appropriate models for translational malaria research.

Brucella spp. and Trypanosoma cruzi are two intracellular pathogens that have no evolutionary common origins but share a similar lifestyle as they establish chronic infections for which they have to circumvent the host immune response. Both pathogens have a virulence factor (prpA in Brucella and tcPrac in T. cruzi) that induces B-cell proliferation and promotes the establishment of the chronic phase of the infectious process. We show here that, even though PrpA promotes B-cell proliferation, it targets macrophages in vitro and is translocated to the cytoplasm during the intracellular replication phase. We observed that PrpA-treated macrophages induce the secretion of a soluble factor responsible for B-cell proliferation and identified nonmuscular myosin IIA (NMM-IIA) as a receptor required for binding and function of this virulence factor. Finally, we show that the Trypanosoma cruzi homologue of PrpA also targets macrophages to induce B-cell proliferation through the same receptor, indicating that this virulence strategy is conserved between a bacterial and a protozoan pathogen.