Alterations in plasma protein N-glycosylation after caloric restriction and bariatric surgery.

BACKGROUND: Protein glycosylation is an enzymatic process known to reflect an individual's physiologic state and changes thereof. The impact of metabolic interventions on plasma protein N-glycosylation has only been sparsely investigated. OBJECTIVE: To examine alterations in plasma protein N-glycosylation following changes in caloric intake and bariatric surgery. SETTING: University of Texas Southwestern Medical Center, US and Oxford University Hospitals, UK. METHODS: This study included 2 independent patient cohorts that recruited 10 and 37 individuals with obesity undergoing a period of caloric restriction followed by bariatric surgery. In both cohorts, clinical data were collated, and the composition of plasma protein N-glycome was analyzed chromatographically. Linear mixed models adjusting for age, sex, and multiple testing (false discovery rate <.05) were used to investigate longitudinal changes in glycosylation features and metabolic clinical markers. RESULTS: A low-calorie diet resulted in a decrease in high-branched trigalactosylated and trisialylated plasma N-glycans and a concomitant increase in low-branched N-glycans in both cohorts. Participants from one cohort additionally underwent a washout period during which caloric intake and body weight increased, resulting in reversal of the initial low-calorie diet-related changes in the plasma N-glycome. Immediate postoperative follow-up revealed the same pattern of N-glycosylation changes in both cohorts-an increase in complex, high-branched, antennary fucosylated, extensively galactosylated and sialylated N-glycans and a substantial decline in simpler, low-branched, core fucosylated, bisected, agalactosylated, and asialylated glycans. A 12-month postoperative monitoring in one cohort showed that N-glycan complexity declines while low branching increases. CONCLUSIONS: Plasma protein N-glycosylation undergoes extensive alterations following caloric restriction and bariatric surgery. These comprehensive changes may reflect the varying inflammatory status of the individual following dietary and surgical interventions and subsequent weight loss.

[Factors associated with the development of malnutrition due to excess in children]. / Factores asociados al desarrollo de malnutrición por exceso en niños.

INTRODUCTION: malnutrition due to excess is a serious public health problem currently affecting 53 % of children and adolescents in Chile. The early identification of associated factors is key in prevention and necessary to guide interventions from early stages of life. OBJECTIVE: to identify factors associated with the development of malnutrition due to excess in three-year-old children under control at Ancora Family Health. METHODS: a case-control study was carried out in three Ancora Family Health Centers located in the communes of La Pintana and Puente Alto; it included 133 children and their mothers. Factors dependent on the child and the mother were analyzed and their importance in the development of malnutrition due to excess was determined. RESULTS: logistic regression showed maternal smoking during pregnancy as a risk factor (OR = 4.065, 95 % CI: 1.119-14.770, p = 0.033) and as protective factors birth weight < 4,000 g (OR = 0.112, 95 % CI: 0.026-0.483, p = 0.003) and weight gain during the first year of life < 6.4 kg in women and < 6.9 kg in men (OR = 0.060, 95 % CI: 0.017-0.210, p = 0.000). CONCLUSIONS: the most important risk factor was maternal smoking and the protective factors were birth weight and weight gain in the first year. Health programs and public policies should focus on modifiable factors such as smoking during pregnancy and adequate weight gain in the first year of life.

Epithelial immune activation and intracellular invasion by non-typeable Haemophilus influenzae.

Type-2 low asthma affects 30-50% of people with severe asthma and includes a phenotype characterized by sputum neutrophilia and resistance to corticosteroids. Airways inflammation in type-2 low asthma or COPD is potentially driven by persistent bacterial colonization of the lower airways by bacteria such as non-encapsulated Haemophilus influenzae (NTHi). Although pathogenic in the lower airways, NTHi is a commensal of the upper airways. It is not known to what extent these strains can invade airway epithelial cells, persist intracellularly and activate epithelial cell production of proinflammatory cytokines, and how this differs between the upper and lower airways. We studied NTHi infection of primary human bronchial epithelial cells (PBECs), primary nasal epithelial cells (NECs) and epithelial cell lines from upper and lower airways. NTHi strains differed in propensity for intracellular and paracellular invasion. We found NTHi was internalized within PBECs at 6 h, but live intracellular infection did not persist at 24 h. Confocal microscopy and flow cytometry showed NTHi infected secretory, ciliated and basal PBECs. Infection of PBECs led to induction of CXCL8, interleukin (IL)-1ß, IL-6 and TNF. The magnitude of cytokine induction was independent of the degree of intracellular invasion, either by differing strains or by cytochalasin D inhibition of endocytosis, with the exception of the inflammasome-induced mediator IL-1ß. NTHi-induced activation of TLR2/4, NOD1/2 and NLR inflammasome pathways was significantly stronger in NECs than in PBECs. These data suggest that NTHi is internalized transiently by airway epithelial cells and has capacity to drive inflammation in airway epithelial cells.

Síndrome de burnout en docentes de salud de Universidades en Chile durante la pandemia de COVID-19 / Burnout syndrome in university health teachers in Chile during the COVID-19 pandemic

Objetivos: El objetivo fue evaluar el Síndrome de Burnout en docentes de ciencias de la salud de Universidades en Chile durante la pandemia de COVID-19. Material y Métodos: Se realizó un estudio cuantitativo, observacional y transversal. Resultados: La prevalencia de SB fue de 4,4. Todas las correlaciones fueron débiles, destacando edad y número de hijos (r = 0,435), edad y horas dedicadas a actividades relacionadas con los hijos (r = 0,451). El promedio de la dimensión agotamiento emocional y realización personal es nivel medio y la despersonalización bajo. Se encontraron diferencias significativas entre hombres y mujeres en agotamiento emocional con medias de 21,85 (DS 11,54) v/s 26,02 (DS 10,79), respectivamente Conclusión: Los resultados muestran diferencias entre hombres y mujeres en la dimensión de agotamiento emocional y, además relaciones entre la edad y número de hijos, y número de hijos y la cantidad de horas destinadas a ellos (AU)

Objectives: The objective was to evaluate the Burnout Syndrome in health sciences teachers from Universities in Chile during the COVID-19 pandemic. Material and Methods: A quantitative, observational and cross-sectional study was carried out. Results: The prevalence of BS was 4.4. All the correlations were weak, highlighting age and number of children (r = 0.435), age and hours spent on activities related to their children (r = 0.451). The average level of emotional exhaustion and personal fulfillment dimension is medium and depersonalization low. Significant differences were found between men and women in emotional exhaustion with means of 21.85 (SD 11.54) v / s 26.02 (SD 10.79), respectively Conclusion: The results show differences between men and women in the dimension of emotional exhaustion and, in addition to relationships between age and number of children, and number of children and the number of hours devoted to them (AU)

Extensive weight loss reduces glycan age by altering IgG N-glycosylation.

BACKGROUND: Obesity, a major global health problem, is associated with increased cardiometabolic morbidity and mortality. Protein glycosylation is a frequent posttranslational modification, highly responsive to inflammation and ageing. The prospect of biological age reduction, by changing glycosylation patterns through metabolic intervention, opens many possibilities. We have investigated whether weight loss interventions affect inflammation- and ageing-associated IgG glycosylation changes, in a longitudinal cohort of bariatric surgery patients. To support potential findings, BMI-related glycosylation changes were monitored in a longitudinal twins cohort. METHODS: IgG N-glycans were chromatographically profiled in 37 obese patients, subjected to low-calorie diet, followed by bariatric surgery, across multiple timepoints. Similarly, plasma-derived IgG N-glycan traits were longitudinally monitored in 1680 participants from the TwinsUK cohort. RESULTS: Low-calorie diet induced a marked decrease in the levels of IgG N-glycans with bisecting GlcNAc, whose higher levels are usually associated with ageing and inflammatory conditions. Bariatric surgery resulted in extensive alterations of the IgG N-glycome that accompanied progressive weight loss during 1-year follow-up. We observed a significant increase in digalactosylated and sialylated glycans, and a substantial decrease in agalactosylated and core fucosylated IgG N-glycans (adjusted p value range 7.38 × 10-04-3.94 × 10-02). This IgG N-glycan profile is known to be associated with a younger biological age and reflects an enhanced anti-inflammatory IgG potential. Loss of BMI over a 20 year period in the TwinsUK cohort validated a weight loss-associated agalactosylation decrease (adjusted p value 1.79 × 10-02) and an increase in digalactosylation (adjusted p value 5.85 × 10-06). CONCLUSIONS: Altogether, these findings highlight that weight loss substantially affects IgG N-glycosylation, resulting in reduced glycan and biological age.

T cell assays differentiate clinical and subclinical SARS-CoV-2 infections from cross-reactive antiviral responses.

Identification of protective T cell responses against SARS-CoV-2 requires distinguishing people infected with SARS-CoV-2 from those with cross-reactive immunity to other coronaviruses. Here we show a range of T cell assays that differentially capture immune function to characterise SARS-CoV-2 responses. Strong ex vivo ELISpot and proliferation responses to multiple antigens (including M, NP and ORF3) are found in 168 PCR-confirmed SARS-CoV-2 infected volunteers, but are rare in 119 uninfected volunteers. Highly exposed seronegative healthcare workers with recent COVID-19-compatible illness show T cell response patterns characteristic of infection. By contrast, >90% of convalescent or unexposed people show proliferation and cellular lactate responses to spike subunits S1/S2, indicating pre-existing cross-reactive T cell populations. The detection of T cell responses to SARS-CoV-2 is therefore critically dependent on assay and antigen selection. Memory responses to specific non-spike proteins provide a method to distinguish recent infection from pre-existing immunity in exposed populations.

A haemagglutination test for rapid detection of antibodies to SARS-CoV-2.

Serological detection of antibodies to SARS-CoV-2 is essential for establishing rates of seroconversion in populations, and for seeking evidence for a level of antibody that may be protective against COVID-19 disease. Several high-performance commercial tests have been described, but these require centralised laboratory facilities that are comparatively expensive, and therefore not available universally. Red cell agglutination tests do not require special equipment, are read by eye, have short development times, low cost and can be applied at the Point of Care. Here we describe a quantitative Haemagglutination test (HAT) for the detection of antibodies to the receptor binding domain of the SARS-CoV-2 spike protein. The HAT has a sensitivity of 90% and specificity of 99% for detection of antibodies after a PCR diagnosed infection. We will supply aliquots of the test reagent sufficient for ten thousand test wells free of charge to qualified research groups anywhere in the world.

Overexpression of Cancer-Associated Stem Cell Gene OLFM4 in the Colonic Epithelium of Patients With Primary Sclerosing Cholangitis.

BACKGROUND: To examine immune-epithelial interactions and their impact on epithelial transformation in primary sclerosing cholangitis-associated ulcerative colitis (PSC-UC) using patient-derived colonic epithelial organoid cultures (EpOCs). METHODS: The EpOCs were originated from colonic biopsies from patients with PSC-UC (n = 12), patients with UC (n = 14), and control patients (n = 10) and stimulated with cytokines previously associated with intestinal inflammation (interferon (IFN) γ and interleukin (IL)-22). Markers of cytokine downstream pathways, stemness, and pluripotency were analyzed by real-time quantitative polymerase chain reaction and immunofluorescence. The OLFM4 expression in situ was assessed by RNAscope and immunohistochemistry. RESULTS: A distinct expression of stem cell-associated genes was observed in EpOCs derived from patients with PSC-UC, with lower expression of the classical stem-cell marker LGR5 and overexpression of OLFM4, previously associated with pluripotency and early stages of neoplastic transformation in the gastrointestinal and biliary tracts. High levels of OLFM4 were also found ex vivo in colonic biopsies from patients with PSC-UC. In addition, IFNγ stimulation resulted in the downregulation of LGR5 in EpOCs, whereas higher expression of OLFM4 was observed after IL-22 stimulation. Interestingly, expression of the IL-22 receptor, IL22RA1, was induced by IFNγ, suggesting that a complex interplay between these cytokines may contribute to carcinogenesis in PSC-UC. CONCLUSIONS: Higher expression of OLFM4, a cancer stemness gene induced by IL-22, is present in PSC-UC, suggesting that IL-22 responses may result in alterations of the intestinal stem-cell niche in these patients.

Tissue-dependent transcriptional and bacterial associations in primary sclerosing cholangitis-associated inflammatory bowel disease.

Background: Primary sclerosing cholangitis (PSC) is a disease of the bile duct and liver. However, patients frequently have co-morbidities including inflammatory bowel disease (IBD) and colorectal cancer. Colorectal cancer risk in patients with PSC-associated ulcerative colitis (PSC/UC) is elevated relative to patients with ulcerative colitis (UC) alone, reasons for which remain obscure. Further, clinical and immunological features, and involved intestinal sites differ between PSC/UC and UC. Understanding the molecular and microbial basis for differences in cancer risk between these two patient groups and how these differ across intestinal sites is important for the development of therapies to prevent colorectal cancer development in at-risk individuals.   Methods: We employed ribonucleic acid sequencing (RNA-seq) analysis of biopsy samples across three intestinal tissue locations (ileum, caecum and rectum) in patients with PSC/UC (n = 8), UC (n = 10) and healthy controls (n = 12) to determine tissue-dependent transcriptional alterations in PSC/UC. We also performed 16S ribosomal RNA (rRNA) amplicon sequencing to determine bacterial associations with PSC/UC and host-microbiome associations. Results: Tissue-defining transcriptional signatures revealed that the ileum was enriched for genes involved in lipid and drug metabolism, the caecum for activated immune cells and the rectum for enteric neurogenesis. Transcriptional alterations relative to healthy control samples were largely shared between patients with PSC/UC or UC although were distinct across tissue locations. Nevertheless, we observed reduced expression of gamma-glutamyl transferase 1 ( GGT1) specifically in the ileum and caecum of patients with PSC/UC. Analysis of the bacterial component of the microbiome revealed high inter-individual variability of microbiome composition and little evidence for tissue-dependency. We observed a reduction in Parabacteroides relative abundance in the rectum of patients with PSC/UC. Conclusions: The role of gamma-glutamyl transferase in maintaining the redox environment through the glutathione salvage pathway makes our observed alterations a potential pathway to PSC-associated colorectal cancer.

Deconvolution of monocyte responses in inflammatory bowel disease reveals an IL-1 cytokine network that regulates IL-23 in genetic and acquired IL-10 resistance.

OBJECTIVE: Dysregulated immune responses are the cause of IBDs. Studies in mice and humans suggest a central role of interleukin (IL)-23-producing mononuclear phagocytes in disease pathogenesis. Mechanistic insights into the regulation of IL-23 are prerequisite for selective IL-23 targeting therapies as part of personalised medicine. DESIGN: We performed transcriptomic analysis to investigate IL-23 expression in human mononuclear phagocytes and peripheral blood mononuclear cells. We investigated the regulation of IL-23 expression and used single-cell RNA sequencing to derive a transcriptomic signature of hyperinflammatory monocytes. Using gene network correlation analysis, we deconvolved this signature into components associated with homeostasis and inflammation in patient biopsy samples. RESULTS: We characterised monocyte subsets of healthy individuals and patients with IBD that express IL-23. We identified autosensing and paracrine sensing of IL-1α/IL-1ß and IL-10 as key cytokines that control IL-23-producing monocytes. Whereas Mendelian genetic defects in IL-10 receptor signalling induced IL-23 secretion after lipopolysaccharide stimulation, whole bacteria exposure induced IL-23 production in controls via acquired IL-10 signalling resistance. We found a transcriptional signature of IL-23-producing inflammatory monocytes that predicted both disease and resistance to antitumour necrosis factor (TNF) therapy and differentiated that from an IL-23-associated lymphocyte differentiation signature that was present in homeostasis and in disease. CONCLUSION: Our work identifies IL-10 and IL-1 as critical regulators of monocyte IL-23 production. We differentiate homeostatic IL-23 production from hyperinflammation-associated IL-23 production in patients with severe ulcerating active Crohn's disease and anti-TNF treatment non-responsiveness. Altogether, we identify subgroups of patients with IBD that might benefit from IL-23p19 and/or IL-1α/IL-1ß-targeting therapies upstream of IL-23.

Gas hydrate versus seabed morphology offshore Lebu (Chilean margin).

Gas-hydrate occurrences along the Chilean margin have been widely documented, but the processes associated with fluid escapes caused by the dissociation of gas hydrates are still unknown. We report a seabed morphology growth related to fluid migration offshore Lebu associated with mud cones by analysing oxygen and deuterium stable water isotopes in pore water, bathymetric, biological and sedimentological data. A relief was observed at - 127 m water depth with five peaks. Enrichment values of δ18O (0.0-1.8‰) and δD (0.0-5.6‰) evidenced past hydrate melting. The orientation of the relief could be associated with faults and fractures, which constitute pathways for fluid migration. The benthic foraminifera observed can be associated with cold seep areas. We model that the mud cones correspond to mud growing processes related to past gas-hydrate dissociation. The integration of (i) the seismic data analysis performed in the surrounding area, (ii) the orientation of our studied relief, (iii) the infaunal foraminifera observed, (iv) the grain size and (v) the total organic matter and isotope values revealed that this area was formerly characterised by the presence of gas hydrates. Hence, this part of the Chilean margin represents a suitable area for investigating fluid-migration processes.

SARS-CoV-2 RNA detected in blood products from patients with COVID-19 is not associated with infectious virus.

Background: Laboratory diagnosis of SARS-CoV-2 infection (the cause of COVID-19) uses PCR to detect viral RNA (vRNA) in respiratory samples. SARS-CoV-2 RNA has also been detected in other sample types, but there is limited understanding of the clinical or laboratory significance of its detection in blood. Methods: We undertook a systematic literature review to assimilate the evidence for the frequency of vRNA in blood, and to identify associated clinical characteristics. We performed RT-PCR in serum samples from a UK clinical cohort of acute and convalescent COVID-19 cases (n=212), together with convalescent plasma samples collected by NHS Blood and Transplant (NHSBT) (n=462 additional samples). To determine whether PCR-positive blood samples could pose an infection risk, we attempted virus isolation from a subset of RNA-positive samples. Results: We identified 28 relevant studies, reporting SARS-CoV-2 RNA in 0-76% of blood samples; pooled estimate 10% (95%CI 5-18%). Among serum samples from our clinical cohort, 27/212 (12.7%) had SARS-CoV-2 RNA detected by RT-PCR. RNA detection occurred in samples up to day 20 post symptom onset, and was associated with more severe disease (multivariable odds ratio 7.5). Across all samples collected ≥28 days post symptom onset, 0/494 (0%, 95%CI 0-0.7%) had vRNA detected. Among our PCR-positive samples, cycle threshold (ct) values were high (range 33.5-44.8), suggesting low vRNA copy numbers. PCR-positive sera inoculated into cell culture did not produce any cytopathic effect or yield an increase in detectable SARS-CoV-2 RNA. Conclusions: vRNA was detectable at low viral loads in a minority of serum samples collected in acute infection, but was not associated with infectious SARS-CoV-2 (within the limitations of the assays used). This work helps to inform biosafety precautions for handling blood products from patients with current or previous COVID-19.

Diferencias de género en matemáticas y lengua: rendimiento académico, autoconcepto y expectativas / Predictive capacity of emotional intelligence on perceived social support of adolescents

Resumen Estudios previos muestran diferencias de género en el rendimiento de matemáticas y lengua, principalmente en adolescentes. Este estudio tiene como objetivo evaluar las diferencias de género en autoconcepto, valor subjetivo, expectativas y rendimiento académico; analizar las relaciones entre las variables y conocer el papel que ellas desempeñan en la explicación del rendimiento en lengua y matemáticas. Participaron 406 estudiantes de 4º y 5º de primaria en Colombia. Los resultados muestran que las niñas presentan mayores expectativas de rendimiento en matemáticas y lengua, así como un rendimiento en lengua superior a los niños. No se encontraron diferencias de género en el autoconcepto y el valor subjetivo de la tarea. El autoconcepto, las expectativas de rendimiento y la edad, explicaron el rendimiento tanto en matemáticas como en lengua. Se discuten las implicaciones de estos resultados para la disminución de la brecha de género en el aprendizaje. Como este estudio es un primer intento de explorar las relaciones entre las creencias de expectativa y valores de las tareas en matemática y lengua con base en el Modelo de Expectativa-Valor en estudiantes hispanos en primaria, se necesita más investigación para apoyar o refutar estos hallazgos.

Abstract Previous studies show gender differences in math and language performance, mainly in adolescents. In this study, we aim to evaluate gender differences in self-concept, subjective value, expectations and academic performance, to analyze the relationships between the variables, and to understand their role in explaining performance in language and mathematics. A total of 406 4th and 5th grade students from Colombia participated in this study. The results show that girls have higher performance expectations in mathematics and language, as well as higher performance in language than boys. No gender differences were found in self-concept and the subjective value of the task. Self-concept, performance expectations and age explained performance in both mathematics and language. We discuss the implications of these results for narrowing the gender gap in learning. Because this study is the first attempt to explore the relationships between expectations and task-value beliefs in language and mathematics in Hispanic primary school students based on the Expectancy-Value Model, more research is needed to support or refute our findings.

Lymphocyte Activation Gene (LAG)-3 Is Associated With Mucosal Inflammation and Disease Activity in Ulcerative Colitis.

BACKGROUND AND AIMS: Lymphocyte activation gene [LAG]-3 is an immune checkpoint and its expression identifies recently activated lymphocytes that may contribute to inflammation. We investigated the role of LAG-3 by analysing its expression and function in immune cells from blood and tissue of patients with ulcerative colitis [UC]. METHODS: The phenotypic properties of LAG-3+ T cells were determined by flow cytometry, qRT-PCR and single-cell RNA-sequencing. LAG-3+ cells were quantified and correlated with disease activity. The functional effects of LAG-3+ cells were tested using a depleting anti-LAG-3 monoclonal antibody [mAb] in a mixed lymphocyte reaction [MLR]. RESULTS: LAG-3+ cells in the blood were negligible. LAG-3+ lymphocytes were markedly increased in inflamed mucosal tissue and both frequencies of LAG-3+ T cells and transcript levels of LAG3 correlated with endoscopic severity. LAG-3 expression was predominantly on effector memory T cells, and single-cell RNA-sequencing revealed LAG3 expression in activated and cytokine-producing T cell subsets. Foxp3+CD25hi Tregs also expressed LAG-3, although most mucosal Tregs were LAG-3-. Mucosal LAG-3+ cells produced mainly interferon γ [IFNγ] and interleukin-17A. LAG-3+ cell numbers decreased in patients who responded to biologics, and remained elevated in non-responders. Treatment with a depleting anti-LAG-3 mAb led to a reduction in proliferation and IFNγ production in an MLR. CONCLUSIONS: LAG-3+ cells are increased in the inflamed mucosa, predominantly on effector memory T cells with an activated phenotype and their cell numbers positively correlate with disease activity. Depleting LAG-3 eliminates activated proliferating T cells, and hence LAG-3 could be a therapeutic target in UC.

TCR and Inflammatory Signals Tune Human MAIT Cells to Exert Specific Tissue Repair and Effector Functions.

MAIT cells are an unconventional T cell population that can be activated through both TCR-dependent and TCR-independent mechanisms. Here, we examined the impact of combinations of TCR-dependent and TCR-independent signals in human CD8+ MAIT cells. TCR-independent activation of these MAIT cells from blood and gut was maximized by extending the panel of cytokines to include TNF-superfamily member TL1A. RNA-seq experiments revealed that TCR-dependent and TCR-independent signals drive MAIT cells to exert overlapping and specific effector functions, affecting both host defense and tissue homeostasis. Although TCR triggering alone is insufficient to drive sustained activation, TCR-triggered MAIT cells showed specific enrichment of tissue-repair functions at the gene and protein levels and in in vitro assays. Altogether, these data indicate the blend of TCR-dependent and TCR-independent signaling to CD8+ MAIT cells may play a role in controlling the balance between healthy and pathological processes of tissue inflammation and repair.

The Short Chain Fatty Acid Butyrate Imprints an Antimicrobial Program in Macrophages.

Host microbial cross-talk is essential to maintain intestinal homeostasis. However, maladaptation of this response through microbial dysbiosis or defective host defense toward invasive intestinal bacteria can result in chronic inflammation. We have shown that macrophages differentiated in the presence of the bacterial metabolite butyrate display enhanced antimicrobial activity. Butyrate-induced antimicrobial activity was associated with a shift in macrophage metabolism, a reduction in mTOR kinase activity, increased LC3-associated host defense and anti-microbial peptide production in the absence of an increased inflammatory cytokine response. Butyrate drove this monocyte to macrophage differentiation program through histone deacetylase 3 (HDAC3) inhibition. Administration of butyrate induced antimicrobial activity in intestinal macrophages in vivo and increased resistance to enteropathogens. Our data suggest that (1) increased intestinal butyrate might represent a strategy to bolster host defense without tissue damaging inflammation and (2) that pharmacological HDAC3 inhibition might drive selective macrophage functions toward antimicrobial host defense.

CD161 Defines a Functionally Distinct Subset of Pro-Inflammatory Natural Killer Cells.

CD161 is a C-type lectin-like receptor expressed on the majority of natural killer (NK) cells; however, the significance of CD161 expression on NK cells has not been comprehensively investigated. Recently, we found that CD161 expression identifies a transcriptional and innate functional phenotype that is shared across various T cell populations. Using mass cytometry and microarray experiments, we demonstrate that this functional phenotype extends to NK cells. CD161 marks NK cells that have retained the ability to respond to innate cytokines during their differentiation, and is lost upon cytomegalovirus-induced maturation in both healthy and human immunodeficiency virus (HIV)-infected patients. These pro-inflammatory NK cells are present in the inflamed lamina propria where they are enriched for integrin CD103 expression. Thus, CD161 expression identifies NK cells that may contribute to inflammatory disease pathogenesis and correlates with an innate responsiveness to cytokines in both T and NK cells.