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Mucosal Immunology Jun 2024Mycobacterium tuberculosis- (Mtb) infected neutrophils are often found in the airways of patients with active tuberculosis (TB), and excessive recruitment of neutrophils...
Mycobacterium tuberculosis- (Mtb) infected neutrophils are often found in the airways of patients with active tuberculosis (TB), and excessive recruitment of neutrophils to the lung is linked to increased bacterial burden and aggravated pathology in TB. The basis for the permissiveness of neutrophils for Mtb and the ability to be pathogenic in TB has been elusive. Here, we identified metabolic and functional features of neutrophils that contribute to their permissiveness in Mtb infection. Using single-cell metabolic and transcriptional analyses, we found that neutrophils in the Mtb-infected lung displayed elevated mitochondrial metabolism, which was largely attributed to the induction of activated neutrophils with enhanced metabolic activities. The activated neutrophil subpopulation was also identified in the lung granulomas from Mtb-infected non-human primates. Functionally, activated neutrophils harbored more viable bacteria and displayed enhanced lipid uptake and accumulation. Surprisingly, we found that IFNγ promoted the activation of lung neutrophils during Mtb infection. Lastly, perturbation of lipid uptake pathways selectively compromised Mtb survival in activated neutrophils. These findings suggest that neutrophil heterogeneity and metabolic diversity are key to their permissiveness for Mtb, and that metabolic pathways in neutrophils represent potential host-directed therapeutics in TB.
PubMed: 38844208
DOI: 10.1016/j.mucimm.2024.05.007 -
Frontiers in Immunology 2014An increasingly larger fraction of patients with hematological diseases are treated by hematopoietic stem cells transplantation (HSCT) from HLA matched unrelated donors.... (Review)
Review
An increasingly larger fraction of patients with hematological diseases are treated by hematopoietic stem cells transplantation (HSCT) from HLA matched unrelated donors. Polymorphisms of HLA genes represent a major barrier to HSCT because HLA-A, -B, -C and DRB1 incompatibilities confer a higher risk of acute graft-versus-host disease (aGVHD) and mortality. Although >22 million volunteer HLA-typed donors are available worldwide, still a significant number of patients do not find a highly matched HSC donor. Because of the large haplotypic diversity in HLA-B-C associations, incompatibilities occur most frequently at HLA-C, so that unrelated donors with a single HLA-C mismatch often represent the only possible choice. The ratio of HLA-C-mismatched HSCT over the total number of transplants varies from 15 to 30%, as determined in 12 multicenter studies. Six multicenter studies involving >1800 patients have reported a 21-43% increase in mortality risk. By using in vitro cellular assays, a large heterogeneity in T-cell allorecognition has been observed. Yet the permissiveness of individual HLA-C mismatches remains poorly defined. It could be linked to the position and nature of the mismatched residues on HLA-C molecules, but also to variability in the expression levels of the mismatched alleles. The permissive C*03:03-03:04 mismatch is characterized by full compatibility at residues 9, 97, 99, 116, 152, 156, and 163 reported to be key positions influencing T-cell allorecognition. With a single difference among these seven key residues the C*07:01-07:02 mismatch might also be considered by analogy as permissive. High variability of HLA-C expression as determined by quantitative RT-PCR has been observed within individual allotypes and shows some correlation with A-B-C-DRB1 haplotypes. Thus in addition to the position of mismatched amino acid residues, expression level of patient's mismatched HLA-C allotype might influence T-cell allorecognition, with patients low expression-C alleles representing possible permissive mismatches.
PubMed: 24904572
DOI: 10.3389/fimmu.2014.00216 -
BMC Public Health Jan 2022In recent years, the number of adolescents engaging in premarital sex has increased, and an increasing number of childhood sexual abuse (CSA) cases have been reported in...
BACKGROUND
In recent years, the number of adolescents engaging in premarital sex has increased, and an increasing number of childhood sexual abuse (CSA) cases have been reported in China. Many studies have indicated that CSA has a well-established association with risky sexual activities. However, only a limited number of studies have explored possible reasons for this association among middle school students, a population that may engage in premarital sex, which is critical for the development of interventions to prevent risky sexual behavior. Based on random samples of middle school students from a Chinese city, this article investigated the relationship between CSA and students' premarital sexual permissiveness (PSP).
METHODS
In a cross-sectional study conducted between 2016 and 2017 in Luzhou, China, 2292 middle school and high school students aged 12-18 years were recruited by multistage random sampling. All students were administered anonymous questionnaires. Multiple linear regression and binary logistic regression analyses were conducted to analyze the relationship between CSA and PSP.
RESULTS
The prevalence of CSA was 15.4% (354/2292; 95% CI: 14-16.9%). A higher percentage of male respondents (18.2%) than female respondents (12.9%) had experienced CSA. A positive association between CSA and PSP was found among students. Respondents who had suffered CSA exhibited greater PSP, and this relationship was observed in the male sample, female sample and the total student sample in Luzhou (β = - 3.76, P < 0.05; β = - 2.79, P < 0.05; and β = - 2.84, P < 0.05, respectively). Respondents who had suffered CSA were also more likely to express a double standard about premarital sex (odds ratio [OR] =1.41, P < 0.05), especially among male students (odds ratio [OR] =1.63, P < 0.05).
CONCLUSIONS
Sex differences in CSA and the relationship between CSA and PSP were significant among this large sample of middle school students in Luzhou (China). The findings suggest that experiencing CSA may be closely related to youth attitudes toward premarital sex, especially among males. Therefore, it is important to emphasize the prevention of CSA and provide adolescent reproductive health programs to reduce the impact of CSA on sexual cognition and attitude, prevent premarital sex and promote positive attitudes toward sexual equality for middle school students.
Topics: Adolescent; China; Cross-Sectional Studies; Female; Health Knowledge, Attitudes, Practice; Humans; Male; Permissiveness; Sex Offenses; Sexual Behavior; Students; Surveys and Questionnaires
PubMed: 35016651
DOI: 10.1186/s12889-021-12490-1 -
Nutrients Jul 2022Objective: Whether dietary carbohydrate (CHO) or fat is more involved in type 2 diabetes (T2DM) induction uncomplicated by dietary fiber was addressed in a spontaneous...
Objective: Whether dietary carbohydrate (CHO) or fat is more involved in type 2 diabetes (T2DM) induction uncomplicated by dietary fiber was addressed in a spontaneous diabetic model, the diurnal Nile rat that mimics the human condition. Methods: A total of 138 male Nile rats were fed plant-based and animal-based saturated fat where 10% energy as CHO and fat were exchanged across 5 diets keeping protein constant, from 70:10:20 to 20:60:20 as CHO:fat:protein %energy. Diabetes induction was analyzed by: 1. diet composition, i.e., CHO:fat ratio, to study the impact of diet; 2. quintiles of average caloric intake per day to study the impact of calories; 3. quintiles of diabetes severity to study the epigenetic impact on diabetes resistance. Results: High glycemic load (GLoad) was most problematic if coupled with high caloric consumption. Diabetes severity highlighted rapid growth and caloric intake as likely epigenetic factors distorting glucose metabolism. The largest weanling rats ate more, grew faster, and developed more diabetes when the dietary GLoad exceeded their gene-based metabolic capacity for glucose disposal. Diabetes risk increased for susceptible rats when energy intake exceeded 26 kcal/day and the GLoad was >175/2000 kcal of diet and when the diet provided >57% energy as CHO. Most resistant rats ate <25 kcal/day independent of the CHO:fat diet ratio or the GLoad adjusted to body size. Conclusion: Beyond the CHO:fat ratio and GLoad, neither the type of fat nor the dietary polyunsaturated/saturated fatty acid (P/S) ratio had a significant impact, suggesting genetic permissiveness affecting caloric and glucose intake and glucose disposition were key to modulating Nile rat diabetes. Fat became protective by limiting GLoad when it contributed >40% energy and displaced CHO to <50% energy, thereby decreasing the number of diabetic rats and diabetes severity.
Topics: Animals; Blood Glucose; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Dietary Carbohydrates; Dietary Fats; Energy Intake; Glucose; Glycemic Load; Humans; Male; Metabolic Syndrome; Murinae; Permissiveness
PubMed: 35893924
DOI: 10.3390/nu14153064 -
Alcoholism, Clinical and Experimental... Jan 2020Using intergenerational prospective data from the Millennium Cohort Study (MCS), we examine whether parents allowing 14-year-olds to drink alcohol is associated with...
BACKGROUND
Using intergenerational prospective data from the Millennium Cohort Study (MCS), we examine whether parents allowing 14-year-olds to drink alcohol is associated with greater likelihood of early adolescents' heavy episodic drinking (i.e., lifetime, rapid escalation from first drink, and frequent past year), beyond shared risk factors for parental alcohol permissiveness and adolescent alcohol use.
METHODS
The MCS is a unique, contemporary, nationally representative study with mother, father, and child data from infancy through age 14 years (n = 11,485 children and their parents). In a series of multivariate logistic regressions, we estimated whether teenagers whose parents allowed them to drink alcohol (16% of parents said "yes") faced an elevated likelihood of heavy alcohol use at age 14, controlling for a large host of likely child and parent confounders measured when children were age 11. To further assess plausible intergenerational associations of parental alcohol permissiveness and offspring heavy alcohol use, coarsened exact matching (CEM) was used to match 14-year-olds whose parents allowed them to drink alcohol with teens whose parents did not allow them to drink on these childhood antecedent variables.
RESULTS
Adolescents whose parents allowed them to drink had higher odds of heavy drinking (odds ratio [OR] = 2.40; 95% confidence interval [CI] = 1.96 to 2.94), rapidly escalating from initiation to heavy drinking (OR = 1.94; CI = 1.52 to 2.49), and frequent heavy drinking (OR = 2.32; 1.73 to 3.09), beyond child and parent confounders and using CEM methods.
CONCLUSIONS
Adolescents who were allowed to drink were more likely to have transitioned quickly from their first drink to consuming 5 or more drinks at 1 time and to drinking heavily 3 or more times in the past year. Given well-documented harms of adolescent heavy drinking, these results do not support the idea that parents allowing children to drink alcohol inoculates them against alcohol misuse.
Topics: Adolescent; Alcohol Drinking; Alcohol-Related Disorders; Child; Cohort Studies; Female; Humans; Longitudinal Studies; Male; Parent-Child Relations; Parents; Permissiveness; Prospective Studies; Risk Factors; Underage Drinking; United Kingdom
PubMed: 31750959
DOI: 10.1111/acer.14224 -
Viruses Oct 2023Ebola virus disease (EVD) represents a global health threat. The etiological agents of EVD are six species of Orthoebolaviruses, with (EBOV) having the greatest public...
Ebola virus disease (EVD) represents a global health threat. The etiological agents of EVD are six species of Orthoebolaviruses, with (EBOV) having the greatest public health and medical significance. EVD pathogenesis occurs as a result of broad cellular tropism of the virus, robust viral replication and a potent and dysregulated production of cytokines. In vivo, tissue macrophages are some of the earliest cells infected and contribute significantly to virus load and cytokine production. While EBOV is known to infect macrophages and to generate high titer virus in the liver, EBOV infection of liver macrophages, Kupffer cells, has not previously been examined in tissue culture or experimentally manipulated in vivo. Here, we employed primary murine Kupffer cells (KC) and an immortalized murine Kupffer cell line (ImKC) to assess EBOV-eGFP replication in liver macrophages. KCs and ImKCs were highly permissive for EBOV infection and IFN-γ polarization of these cells suppressed their permissiveness to infection. The kinetics of IFN-γ-elicited antiviral responses were examined using a biologically contained model of EBOV infection termed EBOV ΔVP30. The antiviral activity of IFN-γ was transient, but a modest ~3-fold reduction of infection persisted for as long as 6 days post-treatment. To assess the interferon-stimulated gene products (ISGs) responsible for protection, the efficacy of secreted ISGs induced by IFN-γ was evaluated and secreted ISGs failed to block EBOV ΔVP30. Our studies define new cellular tools for the study of EBOV infection that can potentially aid the development of new antiviral therapies. Furthermore, our data underscore the importance of macrophages in EVD pathogenesis and those IFN-γ-elicited ISGs that help to control EBOV infection.
Topics: Animals; Mice; Hemorrhagic Fever, Ebola; Interferon-gamma; Kupffer Cells; Ebolavirus; Interferons; Antiviral Agents
PubMed: 37896854
DOI: 10.3390/v15102077 -
MBio Mar 2015Nipah virus and Hendra virus are emerging, highly pathogenic, zoonotic paramyxoviruses that belong to the genus Henipavirus. They infect humans as well as numerous...
UNLABELLED
Nipah virus and Hendra virus are emerging, highly pathogenic, zoonotic paramyxoviruses that belong to the genus Henipavirus. They infect humans as well as numerous mammalian species. Both viruses use ephrin-B2 and -B3 as cell entry receptors, and following initial entry into an organism, they are capable of rapid spread throughout the host. We have previously reported that Nipah virus can use another attachment receptor, different from its entry receptors, to bind to nonpermissive circulating leukocytes, thereby promoting viral dissemination within the host. Here, this attachment molecule was identified as heparan sulfate for both Nipah virus and Hendra virus. Cells devoid of heparan sulfate were not able to mediate henipavirus trans-infection and showed reduced permissivity to infection. Virus pseudotyped with Nipah virus glycoproteins bound heparan sulfate and heparin but no other glycosaminoglycans in a surface plasmon resonance assay. Furthermore, heparin was able to inhibit the interaction of the viruses with the heparan sulfate and to block cell-mediated trans-infection of henipaviruses. Moreover, heparin was shown to bind to ephrin-B3 and to restrain infection of permissive cells in vitro. Consequently, treatment with heparin devoid of anticoagulant activity improved the survival of Nipah virus-infected hamsters. Altogether, these results reveal heparan sulfate as a new attachment receptor for henipaviruses and as a potential therapeutic target for the development of novel approaches against these highly lethal infections.
IMPORTANCE
The Henipavirus genus includes two closely related, highly pathogenic paramyxoviruses, Nipah virus and Hendra virus, which cause elevated morbidity and mortality in animals and humans. Pathogenesis of both Nipah virus and Hendra virus infection is poorly understood, and efficient antiviral treatment is still missing. Here, we identified heparan sulfate as a novel attachment receptor used by both viruses to bind host cells. We demonstrate that heparin was able to inhibit the interaction of the viruses with heparan sulfate and to block cell-mediated trans-infection of henipaviruses. Moreover, heparin also bound to the viral entry receptor and thereby restricted infection of permissive cells in vitro. Consequently, heparin treatment improved survival of Nipah virus-infected hamsters. These results uncover an important role of heparan sulfate in henipavirus infection and open novel perspectives for the development of heparan sulfate-targeting therapeutic approaches for these emerging infections.
Topics: Animals; Cells, Cultured; Cricetinae; Hendra Virus; Henipavirus Infections; Heparitin Sulfate; Humans; Leukocytes; Nipah Virus; Surface Plasmon Resonance; Survival Analysis; Virus Attachment
PubMed: 25759505
DOI: 10.1128/mBio.02427-14 -
Pathogens (Basel, Switzerland) Nov 2021Viral encephalopathy and retinopathy caused by nervous necrosis virus (NNV), is one of the most threatening viral diseases affecting marine fish worldwide. In vitro...
Viral encephalopathy and retinopathy caused by nervous necrosis virus (NNV), is one of the most threatening viral diseases affecting marine fish worldwide. In vitro propagation of NNV strains is essential for the design of effective control measures. In the present study we analysed both the susceptibility and the permissiveness of five fish cell lines (E-11, GF-1, SAF-1, DLB-1, and SaB-1) to three NNV strains (one RGNNV, one SJNNV, and one reassortant RGNNV/SJNNV). E-11 and DLB-1 were demonstrated to be highly susceptible to NNV strains, with average adsorption efficiency (AE) values higher than 90%. SAF-1 also showed high susceptibility (AE 88%), whereas GF-1 can be regarded as moderately susceptible (AE around 50%). On the contrary, SaB-1 can be considered a poorly susceptible cell line (AE values below 20%). E-11 and GF-1 cell lines provided the highest production rates for RGNNV and RG/SJ (around 10) and both cell lines can be regarded as fully permissive for these viral types. However, the SJNNV production rate in GF-1 was only 17.8 and therefore this cell line should be considered semi-permissive for this genotype. In SAF-1 cells, moderate viral replication was recorded but differences in intracellular and extracellular production suggest that viral progeny was not efficiently released. In DLB-1 and SaB-1 the final viral titres obtained in E-11 were lower than those of the inoculum. However, RNA1 synthesis values seem to indicate that RGNNV replication in DLB-1 and SAF-1 could have been underestimated, probably due to a poor adaptation of the virus grown in these cell lines to E-11. Based on all these results, E-11 seems to be the most appropriate cell for in vitro culture of RGNNV, SJNNV, and reassortant strains.
PubMed: 34959520
DOI: 10.3390/pathogens10121565 -
Obesity Reviews : An Official Journal... Mar 2017Parenting style may be an important determinant of an individual's future weight status. However, reviews that evaluate the relationship between parenting style and... (Review)
Review
BACKGROUND
Parenting style may be an important determinant of an individual's future weight status. However, reviews that evaluate the relationship between parenting style and weight-related outcomes have not focused on prospective studies.
METHODS
We systematically searched PubMed, Embase and PsychInfo for studies published between 1995 and 2016 that evaluated the prospective relationship between parenting style experienced in childhood and subsequent weight outcomes.
RESULTS
We identified 11 prospective cohort studies. Among the eight studies that categorized parenting style into distinct groups (i.e. authoritative, authoritarian, permissive and neglectful), five provided evidence that authoritative parenting was associated with lower body mass index gains. Among the six highest quality studies, four suggested a protective role of authoritative parenting style against adverse weight-related outcomes. However, only one study controlled for a comprehensive set of confounders, and the small number of studies conducted within certain age groups precluded our ability to ascertain critical periods when parenting style is most strongly related to child weight.
CONCLUSIONS
The present literature supports the idea that authoritative parenting may be protective against later overweight and obesity, although findings are mixed. More prospective cohort studies of longer durations, with more sophisticated methods that examine age-varying relationships, and that control for a comprehensive set of confounders, are needed.
Topics: Authoritarianism; Body Mass Index; Body Weight; Databases, Factual; Humans; Obesity; Observational Studies as Topic; Overweight; Parent-Child Relations; Parenting; Parents; Permissiveness
PubMed: 28086262
DOI: 10.1111/obr.12497 -
Substance Use & Misuse 2021Recent reports indicate that simultaneous alcohol and marijuana (SAM) use is a growing health concern among college students. As SAM use consists of both alcohol and...
Recent reports indicate that simultaneous alcohol and marijuana (SAM) use is a growing health concern among college students. As SAM use consists of both alcohol and marijuana, risk factors associated with either can serve as plausible targets by prevention efforts to reduce SAM use. : To explore this, the current study investigated the direct and indirect effects of two established risk factors for drinking on SAM use: perceived parental permissiveness toward drinking and friends' approval toward drinking (injunctive norms). : Incoming first-year students ( = 470) reported parental permissiveness, injunctive norms, alcohol use, and SAM use at baseline (T1) and 5 months later (T2). SAM use was assessed again 15 months post-baseline (T3). Path analysis was conducted to examine whether T2 variables mediated relationships between T1 variables and T3 SAM use. : Results revealed that T2 student alcohol use mediated the effects of T1 parental permissiveness, injunctive norms, and alcohol use on T3 SAM use. : Findings from this study extend research on SAM use by identifying perceived parental permissiveness and injunctive drinking norms as risk factors for SAM use through their effects on alcohol use. Based on these findings, it is plausible that parent-based interventions and interventions targeting peer injunctive norms during the first year of college could be used to effectively prevent or reduce SAM use.
Topics: Alcohol Drinking; Friends; Humans; Marijuana Smoking; Marijuana Use; Peer Group; Students; Universities
PubMed: 34596009
DOI: 10.1080/10826084.2021.1981390