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Deficiency in vitamin D can increase the risk of type 2 diabetes (T2D). Yet, the association between 25-hydroxyvitamin D (25(OH)D) levels and the serum proteome in subjects at risk of T2D remains unknown. This proteomic analysis aimed to examine the correlations between serum proteins and 25(OH)D levels stratified as insufficient (< 50 nmol/l), adequate (50–74·9 nmol/l) and optimal (≥ 75 nmol/l) and (2) to identify biological pathways linked to these proteins that may reduce T2D risk. In this cross-over study, twenty-five hyperinsulinaemic French-Canadian adults from the Quebec City metropolitan area (Canada) were evaluated at four timepoints: before and after 6 weeks of either adequate dairy intake (∼2 servings/d) or high dairy intake (≥ 4 servings/d). Serum 25(OH)D concentrations were measured using an immunoassay, and serum protein profiling was performed using liquid chromatography–tandem MS. Gene ontology analysis identified biological pathways. Dairy intake did not significantly change 25(OH)D serum levels. Nevertheless, in ten subjects with optimal 25(OH)D levels, positively correlated proteins were mainly involved in Ig-mediated immune response, regulation of blood coagulation, acute-phase response and adaptive immunity. Negatively correlated proteins were enriched in classical complement activation, innate immune response, acute-phase response and proteolysis. In six subjects with adequate 25(OH)D levels, correlated proteins were associated mainly with innate immune responses. No significant biological pathway enrichment was observed in subjects with insufficient 25(OH)D. Overall, individuals with higher or optimal serum 25(OH)D levels exhibit a greater number of proteins enriched in various immune system response pathways, processes known to influence T2D development.
Neonates are highly susceptible to infection, a major cause of neonatal death, given their immature immune system. Comprehensive studies examining multiple immune-response-related proteins in relation to neonatal infection are scarce. We conducted a nested case-control study within the Shenzhen Baoan Birth and Twin (SZBBTwin) cohort, measuring 92 immune-response-related proteins in cord plasma of 149 twins (including 34 discordant twin pairs) with proximity extension assay. All twins were followed for clinical diagnoses of infection from birth until 27 days of age. Wilcoxon rank-sum test was used to determine differentially abundant proteins (DAPs) between infected and noninfected neonates, the predictive performance of which was evaluated by receiver operating characteristic curves, and their functions and pathways were annotated through enrichment analysis. Logistic regression was used to assess the associations between levels of proteins and risk of neonatal infection. Finally, five DAPs (ITGA11, FCRL6, DDX58, SH2D1A, and EDAR) were identified for neonatal infection, and the area under the curve of the five DAPs achieved 0.835 for infection prediction. Enrichment analysis indicated that five DAPs were mainly involved in immune function and cell binding, and they were mainly enriched in the nuclear factor kappa-B pathway. A higher level of ITGA11 was associated with an increased risk of neonatal infection in all twins (OR 3.00; 95% CI [1.33, 6.78]) and discordant twin pairs (OR 5.50; 95% CI [1.20, 25.23]). In conclusion, multiple immune-response-related proteins in cord plasma, particularly ITGA11, are associated with the risk of neonatal infection in twins.
Depressive disorder (DD) is a widespread mental illness that lacks objective diagnostic biomarkers, complicating early detection and personalised treatment. This study investigated the diagnostic value of serum interferon-gamma (IFN-γ), nerve growth factor (NGF), and their ratio, alongside thyroid peroxidase antibody (TPOAb) and glial fibrillary acidic protein (GFAP), in patients with DD compared to healthy controls.
Methods:
A total of 238 participants (118 with DD and 120 controls) were enrolled. Depression severity was assessed using DSM-5 and HAM-D criteria. Serum biomarkers were measured using enzyme-linked immunosorbent assays (ELISA), and receiver operating characteristic (ROC) analysis was performed to assess diagnostic performance.
Results:
DD patients exhibited significantly lower IFN-γ and higher NGF levels than controls (both p < 0.001), resulting in a markedly reduced IFN-γ/NGF ratio. The IFN-γ/NGF ratio achieved the highest diagnostic accuracy (AUC = 0.858, sensitivity = 82.20%, specificity = 77.50%), outperforming IFN-γ (AUC = 0.766) and NGF (AUC = 0.848) alone. TPOAb and GFAP levels did not differ significantly between groups.
Conclusion:
The IFN-γ/NGF ratio is a promising biomarker for depressive disorder, offering superior diagnostic accuracy over individual immune or neurotrophic markers. This composite index may support more objective and biologically informed diagnosis in clinical psychiatry.
Dr. C. Norman Coleman’s impact is difficult to measure overall, even if one focuses only on his work as NCI’s Radiation Research Program (RRP) leader. His laboratory work spanned immune-oncology and radiation therapy, RNA biology, normal tissue and tumor tissue radiobiology, and the development of tissue chips for use in radiation biology research. His programmatic leadership helped the RRP develop health equity programs addressing Native American access to optimal cancer care, evaluation of hadron therapy biology, radiation biology, reproducibility and rigor, foundational molecular biology of the tumor and normal tissue caused by radiation therapy dynamically, and global health and security issues. While doing all these things, he found time to mentor countless people in the field, many now leaders, and to read and discuss science across disciplines. He was a dedicated, caring, kind scientist who truly wanted to help and improve the world for others.
C-type lectins (CTLs), a diverse family of pattern recognition receptors, are essential for immune recognition and pathogen clearance in invertebrates. TcCTL17 contains one carbohydrate recognition domain and three scavenger receptor Cys-rich domains. Spatial and temporal expression analysis revealed that TcCTL17 is highly expressed in early pupa, early adult stages, and the larval gut at 20 days. The recombinant TcCTL17 exhibited dose-dependent binding to lipopolysaccharides and peptidoglycans, Ca2+-dependent binding and agglutination of bacteria in vitro. Knocking down TcCTL17 before bacterial exposure reduced survival rates and increased bacterial loads in T. castaneum larvae, accompanied by decreased antimicrobial peptide expression and haemolymph phenoloxidase activity. Additionally, TcCTL17 RNA interference caused developmental abnormalities, affecting metamorphosis and fecundity, possibly by influencing the 20E, JH, and vitellogenin pathways. These findings underscore dual functions of TcCTL17 in immunity and development, making it a potential target for pest management.
This study investigated the co-infection dynamics of Schistosoma mansoni and Ancylostoma ceylanicum in an experimental model. Two experiments were conducted to investigate varying infection orders. In experimental group 1, subjects were initially infected with A. ceylanicum, followed by S. mansoni infection. In group 2, subjects were first infected with S. mansoni, followed by A. ceylanicum infection. The co-infected groups were compared to mono-infected groups for further analysis. Parameters assessed included weight, fecal egg elimination, blood cell counts, IgG response, histopathological analysis, and granuloma morphometry. Results indicated that the timing of infections influenced weight loss. Co-infected animals lost weight similarly to A. ceylanicum-infected animals when A. ceylanicum preceded S. mansoni. The co-infected groups did not experience worsened anemia, despite both parasites being hematophagous. No linear correlation was found between S. mansoni egg counts and anti-SEA IgG production. The response to the S. mansoni adult worm antigen was significantly higher in the S. mansoni mono-infected group compared to the group previously infected with hookworm. Co-infection with A. ceylanicum after S. mansoni infection also interfered with the host response. It caused a delay in the peak of S. mansoni egg elimination compared to the S. mansoni monoinfected group. Additionally, fewer eggs were retained in the liver compared to single infections. These findings help elucidate the interactions between different parasites and their hosts in the same endemic area, providing valuable information to enhance strategies for disease control and management.
Coinfection of a host by more than 1 parasite is more common than single infection in wild environments and can have differing impacts, although coinfections have relatively rarely been quantified. Host immune responses to coinfection can contribute to infection costs but are often harder to predict than those associated with single infection, due to the influence of within-host parasite–parasite interactions on infection virulence. To first quantify coinfection in a common bird species, and then to test for immune-related impacts of coinfection, we investigated the prevalence and immune response to avian haemosporidian (genera: Plasmodium, Haemoproteus and Leucocytozoon) coinfection in wild blackbirds. Coinfection status was diagnosed using a 1-step multiplex polymerase chain reaction, immune response was quantified through white blood cell counts and heterophil: lymphocyte ratios, and parasitaemia was quantified for each infected sample. We detected high rates of haemosporidian infection and coinfection, although neither impacted immune activity, despite a significantly higher parasitaemia in individuals experiencing double vs single infection. This suggests that immune-related costs of haemosporidian single and coinfection are low in this system. This could be due to long-term host–parasite coevolution, which has decreased infection virulence, or a consequence of reduced costs associated with chronic infections compared to acute infections. Alternatively, our results may obscure immune-related costs associated with specific combinations of coinfecting haemosporidian genera, species or lineages. Future research should investigate interactions that occur between haemosporidian parasites within hosts, as well as the ways in which these interactions and resulting impacts may vary depending on parasite identity.
Leishmaniasis, Chagas disease (CD), and Human African Trypanosomiasis (HAT) are neglected tropical diseases in humans caused by intracellular parasites from the class Kinetoplastida. Leishmaniasis is one infectious disease that exhibits sex-bias not explained solely by behavioral or cultural differences. However, HAT and CD have less well documented and understood sex-related differences, either due to a lack of differences or insufficient research and reporting.
Methods
This paper reviews the rate of disease and disease severity among male and females infected with CD, HAT, and leishmaniasis. We further review the specific immune response to each pathogen and potential sex-based mechanisms which could impact immune responses and disease outcomes.
Results
These mechanisms include sex hormone modulation of the immune response, sex-related genetic differences, and socio-cultural factors impacting risky behaviors in men and women. The mechanistic differences in immune response among sexes and pathogens provide important insights and identification of areas for further research.
Conclusions
This information can aid in future development of inclusive, targeted, safe, and effective treatments and control measures for these neglected diseases and other infectious diseases.
Visceral leishmaniasis (VL) is a tropical disease that can be fatal if acute and untreated. Diagnosis is difficult, the treatment is toxic and prophylactic vaccines do not exist. Leishmania parasites express hundreds of proteins and several of them are relevant for the host's immune system. In this context, in the present study, 10 specific T-cell epitopes from 5 parasite proteins, which were identified by antibodies in VL patients’ sera, were selected and used to construct a gene codifying the new chimeric protein called rCHI. The rCHI vaccine was developed and thoroughly evaluated for its potential effectiveness against Leishmania infantum infection. We used monophosphoryl lipid A (MPLA) and polymeric micelles (Mic) as adjuvant and/or delivery system. The results demonstrated that both rCHI/MPLA and rCHI/Mic significantly stimulate an antileishmanial Th1-type cellular response, with higher production of IFN-γ, TNF-α, IL-12 and nitrite in vaccinated animals, and this response was sustained after challenge. In addition, these mice significantly reduced the parasitism in internal organs and increased the production of IgG2a isotype antibodies. In vivo and in vitro toxicity showed that rCHI is safe for the mammalians, and the recombinant protein also induced in vitro lymphoproliferative response and production of Th1-type cytokines by human cells, which were collected from healthy subjects and treated VL patients. These data suggest rCHI plus MPLA or micelles could be considered as a vaccine candidate against VL.
Sperm infertility or subfertility is detrimental to the precious highland germplasm like yak whose population has been gradually declining in India. Understanding the ‘omic’ landscape of infertile or subfertile yak sperm can reveal some interesting insights. In an attempt to do the same, this study considered the semen of infertile or subfertile yak bulls for whole-genome and transcriptome evaluations. DNA sequencing revealed that the yak sperm genome contains the necessary genes to carry out all the important biological processes related to the growth, development, survival and multiplication of an organism. Interestingly, RNA Seq results highlighted that genes like VAMP7, MYLK, ARAP2 and MARCH6 showed increased expression, while biological processes related to immune response (GO:0043308, GO:0002447, GO:0002278, GO:0043307, GO:0043312, GO:0002283, GO:0043299 and GO:0002446) were significantly overrepresented. These findings hint at a possible role played by immune system in regulating infertility or subfertility in yaks. Further, in-depth studies can validate these findings and help in improving our biological understanding in this area.
Pectin is composed of a group of complex polysaccharides that are naturally found in various plants and are associated with a range of beneficial health effects. Health outcomes from dietary pectin can vary depending on botanical origin, dietary dose and structure of pectin. The objective of this scoping review is to build a comprehensive overview of the current evidence available on intervention studies conducted in humans and to better understand the possible knowledge gaps in terms of structure–function relationships across the different health-related effects. PubMed and Embase databases were searched using PRISMA-ScR guidelines, yielding 141 references (from the initial 3704), representing 134 intervention studies performed between 1961 and 2022 that met inclusion criteria. Studies were divided into six categories, which included gut health, glycaemic response and appetite, fat metabolism, bioavailability of micronutrients, immune response and other topics. Review of these human intervention studies identified a variety of cohort characteristics and populations (life stage, health status, country), sources/types of pectin (i.e. citrus, sugarbeet, apple, other and non-defined), intervention timeframes (from one single intake to 168 d) and doses (0.1–50 g/d) that were tested for health outcomes in people. Gut health, post-prandial glucose regulation and maintenance of blood cholesterol represented the largest categories of studied outcomes. Further research to strengthen the structure–function relationships for pectin with health properties and associated outcomes is warranted and will benefit from a more precise description of physico-chemical characteristics and molecular compositions, such as degree of esterification, weight, degree of branching, viscosity, gel formation and solubility.
Edited by
Allan Young, Institute of Psychiatry, King's College London,Marsal Sanches, Baylor College of Medicine, Texas,Jair C. Soares, McGovern Medical School, The University of Texas,Mario Juruena, King's College London
This chapter outlines the current research on the stress response and how chronic stress can lead to the dysfunction of neuroendocrine and immune responses and ultimately contribute to the development of psychiatric disorders. The chapter aims to provide an understanding of the pathways involved in the stress response, in particular the HPA axis and the role of cortisol, exploring the role of HPA hyperactivity as a contributor to major depressive disorder. The chapter reviews the impact of the stress response in bipolar and post-traumatic stress disorder, concluding with a summary of our current understanding of the interplay of mood disorders with early life stress.
For the purpose of this chapter, we are going to frame the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through a targeted and simplistic approach. SARS-CoV-2 invades and infects host cells via interaction of its spike protein with mucosal membrane receptor angiotensin-converting enzyme 2 (ACE2). The immune system response can be quite variable and depends on multiple factors, some specific to the virus and others specific to the patient’s immune competence or clinical comorbidities. SARS-CoV-2 can also be unusually effective at evading the triggering of early innate immune responses, such as type 1 interferons and related molecules. It is possible that much of the nature of COVID-19 as an illness is a consequence of this one evasion trick of SARS-CoV-2. In this chapter, we will describe this immune response and discuss mechanisms by which the virus actively seeks to evade our immune system. We will also discuss how we dissect the body’s immune response to assist us in identifying therapeutic and prophylactic targets and with the development of vaccines, and we will look at the effectiveness of these targets on morbidity and mortality and their adverse reaction profiles.
This prospective study examines the immune response to SARS-CoV-2 vaccination in patients with psychotic disorders compared with healthy volunteers. Participants were recruited naturalistically as part of the UK's COVID-19 vaccination programme. Prior to receiving their first COVID-19 vaccine, blood samples were provided by participants to examine anti-SARS-CoV-2 immunoglobulins (IgG) at baseline, followed by a repeat assay 1 month after receiving their first vaccine to assess vaccine response. The increase of IgG levels from baseline to 1 month post-vaccination was significantly lower in patients compared with controls, supporting evidence of impaired vaccine response in people with psychotic disorders. When excluding patients treated with clozapine from the analysis, this difference was no longer significant, suggesting that effects may be particularly marked in people taking clozapine.
Atlantic salmon (Salmo salar) is repeatedly exposed to and infected with ectoparasitic salmon lice (Lepeophtheirus salmonis) both in farms and in nature. However, this is not reflected in laboratory experiments where fish typically are infected only once. To investigate if a previous lice infection affects host response to subsequent infections, fish received 4 different experimental treatments; including 2 groups of fish that had previously been infected either with adult or infective salmon lice larvae (copepodids). Thereafter, fish in all treatment groups were infected with either a double or a single dose of copepodids originating from the same cohort. Fish were sampled when lice had developed into the chalimus, the pre-adult and the adult stage, respectively. Both the specific growth rate and cortisol levels (i.e. a proxy for stress) of the fish differed between treatments. Lice success (i.e. ability to infect and survive on the host) was higher in naïve than in previously infected fish (pre-adult stage). The expression of immune and wound healing transcripts in the skin also differed between treatments, and most noticeable was a higher upregulation early in the infection in the group previously infected with copepodids. However, later in the infection, the least upregulation was observed in this group, suggesting that previous exposure to salmon lice affects the response of Atlantic salmon towards subsequent lice infections.
Zn is an important trace element involved in various biochemical processes in aquatic species. An 8-week rearing trial was thus conducted to investigate the effects of Zn on juvenile largemouth bass (Micropterus salmoides) by feeding seven diets, respectively, supplemented with no Zn (Con), 60 and 120 mg/kg inorganic Zn (Sul60 and Sul120), and 30, 60, 90 and 120 mg/kg organic Zn (Bio30, Bio60, Bio90 and Bio120). Sul120 and Bio120 groups showed significantly higher weight gain and specific growth rate than Con group, with Bio60 group obtaining the lowest viscerosomatic index and hepatosomatic index. 60 or 90 mg/kg organic Zn significantly facilitated whole body Zn retention. Up-regulation of hepatic superoxide dismutase, glutathione peroxidase and catalase activities and decline of malondialdehyde contents indicated augmented antioxidant capacities by organic Zn. Zn treatment also lowered plasma aminotransferase levels while promoting acid phosphatase activity and hepatic transcription levels of alp1, acp1 and lyz-c than deprivation of Zn. The alterations in whole body and liver crude lipid and plasma TAG contents illustrated the regulatory effect of Zn on lipid metabolism, which could be possibly attributed to the changes in hepatic expressions of acc1, pparγ, atgl and cpt1. These findings demonstrated the capabilities of Zn in potentiating growth and morphological performance, antioxidant capacity, immunity as well as regulating lipid metabolism in M. salmoides. Organic Zn could perform comparable effects at same or lower supplementation levels than inorganic Zn, suggesting its higher efficiency. 60 mg/kg supplementation of organic Zn could effectively cover the requirements of M. salmoides.
The aim of this trial was to describe the behavioural, neuroendocrine, immune and acute phase stress responses in dogs undergoing elective surgery in normal, clinical practice conditions. Sixteen dogs were submitted to elective orchiectomy or ovariohysterectomy using a standardised surgical protocol. Each animal was confined to the Intensive Care Unit during pre- and post-surgery and perioperative behavioural, neuroendocrine, immune and acute phase responses were studied. Behavioural categories, cortisol, prolactin, white blood cell, C-reactive protein and haptoglobin variation were evaluated. Values at different times were compared with basal values shown by the dog in its usual environment. Communicative and explorative behaviours showed high occurrence pre-surgery and were inhibited post-surgery. Decreases in post-surgery activity, interactive behaviours and changes in waking/sleeping patterns were observed. The most sensitive marker of psychological stress, cortisol, in comparison with basal values, showed a significant increase both during pre- and post-surgery confinement in the ICU cage. Prolactin values were characterised by a significant decrease early into the post-surgery period. The immune response was characterised by long-term neutrophilia and monocytosis, but by short-term lymphopaenia and eosinopaenia, limited to the early post-operative period. With regard to the acute phase response, both C-reactive protein and haptoglobin showed a long-term increase, post-surgery. Changes in behavioural, haematological and biochemical markers showed that perioperative stress represents a major challenge to dog welfare.
Wild mammals, especially rodents, can participate in the life cycle of Schistosoma mansoni; however, the impact of these parasite strains on the severity of schistosomiasis remains unclear. The aim of this study was to comparatively evaluate the parasitological and immunopathological alterations induced by an S. mansoni strain isolated from the wild rodent Holochilus sciureus (HS strain) and a parasite strain isolated from a human (LE strain) in experimentally infected mice. Male BALB/c mice were subcutaneously infected with 50 cercariae/mouse of either the HS or the LE strain and were evaluated for 12 weeks. In the experimental groups, the parasite burden was estimated by worm and egg (feces and tissues) count, and immunopathological alterations were evaluated in the liver and intestines. Compared to experimental infection with the LE parasite strain, HS-infected mice showed reduced number of parasite worms but higher fecundity rate, significant reduction in IL-5, IL-10 and IL-13 concentrations, lower EPO-activity in liver homogenate and higher concentrations of TNF-α, IFN-γ, IL-12 and IL-17 in the small intestine homogenate. Moreover, HS infection resulted in higher concentrations of NO end-products in both the liver and intestine, suggesting a predominance of the Th1/Th17 immune response. HS-infected mice also showed higher plasma transaminase levels, formed larger granulomas, and had a higher mortality rate in comparison with LE-infected mice. Data indicate that BALB/c mice infected with the HS strain of S. mansoni showed reduced susceptibility to the parasite but stronger tissue inflammation and high disease severity.
Necrotic enteritis (NE), caused by Clostridium perfringens (CP), is one of the most common of poultry diseases, causing huge economic losses to the poultry industry. This review provides an overview of the pathogenesis of NE in chickens and of the interaction of CP with the host immune system. The roles of management, nutrition, probiotics, and vaccination in reducing the incidence and severity of NE in poultry flocks are also discussed.
An 8-week feeding trial was conducted to investigate the effects of dietary vitamin D3 supplementation on the growth performance, tissue Ca and P concentrations, antioxidant capacity, immune response and lipid metabolism in Litopenaeus vannamei larvae. A total of 720 shrimp (initial weight 0·50 ± 0·01 g) were randomly distributed into six treatments, each of which had three duplicates of forty shrimp per duplicate. Six isonitrogenous and isolipidic diets were formulated to contain graded vitamin D3 (0·18, 0·23, 0·27, 0·48, 0·57 and 0·98 mg/kg of vitamin D3, measured) supplementation levels. The results revealed that L. vannamei fed diet containing 0·48 mg/kg of vitamin D3 achieved the best growth performance. Compared with the control group, supplementing 0·48 mg/kg of vitamin D3 significantly increased (P < 0·05) the activities of catalase, total antioxidative capacity, alkaline phosphatase and acid phosphatase in serum and hepatopancreas. Expression levels of antioxidant and immune-related genes were synchronously increased (P < 0·05). Carapace P and Ca concentrations were increased (P < 0·05) with the increased vitamin D3 supplementation levels. Further analysis of lipid metabolism-related genes expression showed that shrimp fed 0·48 mg of vitamin D3 per kg diet showed the highest value in the expression of lipid synthesis-related genes, while shrimp fed 0·98 mg of vitamin D3 per kg diet showed the highest value in the expression of lipolysis-related genes. In conclusion, the results of present study indicated that dietary supplementation of 0·48 mg/kg of vitamin D3 could increase Ca and P concentrations, improve antioxidant capacity and immune response, and influence lipid metabolism in L. vannamei.