scholarly journals The Immunological Factors Predisposing to Severe Covid-19 Are Already Present in Healthy Elderly and Men

2021 ◽  
Vol 12 ◽  
Author(s):  
Gizem Kilic ◽  
Ozlem Bulut ◽  
Martin Jaeger ◽  
Rob ter Horst ◽  
Valerie A. C. M. Koeken ◽  
...  
Keyword(s):  
The Elderly ◽  
T Cell Subsets ◽  
Older Individuals ◽  
Differential Abundance ◽  
Healthy Elderly ◽  
Different Seasons ◽  
Underlying Causes ◽  
Inflammatory Proteins ◽  
Immunological Factors

Male sex and old age are risk factors for COVID-19 severity, but the underlying causes are unknown. A possible explanation for this might be the differences in immunological profiles in males and the elderly before the infection. With this in mind, we analyzed the abundance of circulating proteins and immune populations associated with severe COVID-19 in 2 healthy cohorts. Besides, given the seasonal profile of COVID-19, the seasonal response against SARS-CoV-2 could also be different in the elderly and males. Therefore, PBMCs of female, male, young, and old subjects in different seasons of the year were stimulated with heat-inactivated SARS-CoV-2 to investigate the season-dependent anti-SARS-CoV-2 immune response. We found that several T cell subsets, which are known to be depleted in severe COVID-19 patients, were intrinsically less abundant in men and older individuals. Plasma proteins increasing with disease severity, including HGF, IL-8, and MCP-1, were more abundant in the elderly and males. Upon in vitro SARS-CoV-2 stimulation, the elderly produced significantly more IL-1RA and had a dysregulated IFNγ response with lower production in the fall compared with young individuals. Our results suggest that the immune characteristics of severe COVID-19, described by a differential abundance of immune cells and circulating inflammatory proteins, are intrinsically present in healthy men and the elderly. This might explain the susceptibility of men and the elderly to SARS-CoV-2 infection.

scholarly journals The Immunological Factors Predisposing To Severe COVID-19 Are Already Present In Healthy Elderly And Men

2021 ◽  
Author(s):  
Gizem Kilic ◽  
Ozlem Bulut ◽  
Martin Jaeger ◽  
Rob ter Horst ◽  
Valerie Koeken ◽  
...  
Keyword(s):  
The Elderly ◽  
T Cell Subsets ◽  
Older Individuals ◽  
Differential Abundance ◽  
Healthy Elderly ◽  
Different Seasons ◽  
Underlying Causes ◽  
Inflammatory Proteins ◽  
Immunological Factors ◽  
Lower Production

Background: Male sex and old age are risk factors for COVID-19 severity, but the underlying causes are unknown. A possible explanation for this might be the differences in immunological profiles in males and the elderly before the infection. Given the seasonal profile of COVID-19, the seasonal response against SARS-CoV-2 could also be different in these groups. Methods: The abundance of circulating proteins and immune populations associated with severe COVID-19 was analyzed in 2 healthy cohorts. PBMCs of female, male, young, and old subjects in different seasons of the year were stimulated with heat-inactivated SARS-CoV-2. Results: Several T cell subsets, which are known to be depleted in severe COVID-19 patients, were intrinsically less abundant in men and older individuals. Plasma proteins increasing with disease severity, including HGF, IL-8, and MCP-1, were more abundant in the elderly and males. The elderly produced significantly more IL-1RA and had a dysregulated IFNγ response with lower production in the summer compared with young individuals. Conclusions: The immune characteristics of severe COVID-19, described by a differential abundance of immune cells and circulating inflammatory proteins, are intrinsically present in healthy men and the elderly. This might explain the susceptibility of men and the elderly to SARS-CoV-2 infection.

scholarly journals Production of interferon-γ by natural killer cells and aging in chronic human schistosomiasis

2004 ◽  
Vol 13 (5-6) ◽  
pp. 327-333 ◽  
Author(s):  
E. Speziali ◽  
J. Bethony ◽  
O. Martins-Filho ◽  
L. A. O. Fraga ◽  
D. S. Lemos ◽  
...  
Keyword(s):  
Natural Killer Cells ◽  
Natural Killer ◽  
Infection Intensity ◽  
The Elderly ◽  
Interferon Γ ◽  
Older Individuals ◽  
Killer Cells ◽  
Human Schistosomiasis ◽  
Ifn Γ

BACKGROUNG: Aging is associated with several alterations in the phenotype, repertoire and activation status of lymphocytes as well as in the cytokine profile produced by these cells. As a lifelong condition, chronic parasitic diseases such as human schistosomiasis overlaps with the aging process and no systematic study has yet addressed the changes in immune response during infection withSchistosoma mansoniin older individuals.Aim: Herein we study the influence of immunological alterations brought about by senescence in the course of schistosomiasis.Materials and methods: Individuals 10-95 years of age, from both sexes, from an endemic area forS. mansoniinfection were matched by intensity of infection as measured by egg counts. We analyzed, as a parameter, cytokine expression by lymphocytes and natural killer cells afterin vitrostimulation with soluble egg antigen and soluble worm antigen using flow cytometry.Results: We demonstrated that the frequency of CD16+interferon-γ (IFN-γ)+natural killer cells in negative individuals over the age of 70 years is significantly higher than in positive individuals afterin vitrostimulation withS. mansoniantigen extracts. The frequency of these cells is increased in all individuals over the age of 50 years and only declines in positive individuals after 70 years of age. Analysis of either CD4?or CD8?cells after antigen stimulation show no significant increase in frequency of IFN-γ in negative or in positive individuals of this age group, suggesting that the effect on CD16+cells is not T-cell dependent.Conclusion: Since production of IFN-γ has been related to resistance to schistosome infection, our data suggest that age-associated changes in CD16+cells may play a role in controlling infection intensity in the elderly inS. mansoniendemic areas of Brazil.

scholarly journals Abnormal phenotypic distribution of regulatory and effector T cells in octogenarian and nonagenarian women

2015 ◽  
Vol 61 (4) ◽  
pp. 329-335
Author(s):  
Wilson de Melo Cruvinel ◽  
Danilo Mesquita Júnior ◽  
Júlio Antônio Pereira Araújo ◽  
Karina Carvalho Samazi ◽  
Esper Georges Kállas ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Mononuclear Cells ◽  
Elderly Women ◽  
The Elderly ◽  
Effector T Cells ◽  
T Cell Subsets ◽  
Healthy Elderly ◽  
T Cell Phenotypes ◽  
Effects Of Aging

SummaryIntroduction:aging is associated with several immunologic changes. Regulatory (Treg) and effector T cells are involved in the pathogenesis of infectious, neoplastic, and autoimmune diseases. Little is known about the effects of aging on the frequency and function of these T cell subpopulations.Methods:peripheral blood mononuclear cells (PBMC) were obtained from 26 young (under 44 years old) and 18 elderly (above 80 years old) healthy women. T cell subpopulations were analyzed by flow cytometry.Results:elderly individuals had lower frequency of several activated effector T cell phenotypes as compared with young individuals: CD3+CD4+CD25+ (3.82±1.93 versus 9.53±4.49; p<0.0001); CD3+CD4+CD25+CD127+(2.39±1.19 versus 7.26±3.84; p<0.0001); CD3+CD4+CD25+ (0.41±0.22 versus 1.86±0.85, p<0.0001); and CD3+CD4+CD25highCD127+(0.06±0.038 versus 0.94±0.64, p<0.0001). Treg (CD3+CD4+CD25+CD127øFoxp3+) presented lower frequency in elderly individuals as compared to young adults (0.34±0.18 versus 0.76±0.48; p=0.0004) and its frequency was inversely correlated with age in the whole group (r=-0.439; p=0.013). The elderly group showed higher frequency of two undefined CD25øFoxp3+ phenotypes: CD3+CD4+CD25øFoxp3+(15.05±7.34 versus 1.65±1.71; p<0.0001) and CD3+CD4+CD25øCD127øFoxp3+(13.0±5.52 versus 3.51±2.87; p<0.0001).Conclusions:the altered proportion of different T cell subsets herein documented in healthy elderly women may be relevant to the understanding of the immunologic behavior and disease susceptibility patterns observed in geriatric patients.

Nonexercise movement in elderly compared with young people

2007 ◽  
Vol 292 (4) ◽  
pp. E1207-E1212 ◽  
Author(s):  
Ann M. Harris ◽  
Lorraine M. Lanningham-Foster ◽  
Shelly K. McCrady ◽  
James A. Levine
Keyword(s):  
Energy Expenditure ◽  
Lean Body Mass ◽  
Body Mass ◽  
The Elderly ◽  
Energetic Cost ◽  
Elderly Subjects ◽  
Older Individuals ◽  
Free Living ◽  
Healthy Elderly ◽  
Young Subjects

The association between free-living daily activity and aging is unclear because nonexercise movement and its energetic equivalent, nonexercise activity thermogenesis, have not been exhaustively studied in the elderly. We wanted to address the hypothesis that free-living nonexercise movement is lower in older individuals compared with younger controls matched for lean body mass. Ten lean, healthy, sedentary elderly and 10 young subjects matched for lean body mass underwent measurements of nonexercise movement and body posture over 10 days using sensitive, validated technology. In addition, energy expenditure was assessed using doubly labeled water and indirect calorimetry. Total nonexercise movement (acceleration arbitrary units), standing time, and standing acceleration were significantly lower in the elderly subjects; this was specifically because the elderly walked less distance per day despite having a similar number of walking bouts per day compared with the young individuals. The energetic cost of basal metabolic rate, thermic effect of food, total daily energy expenditure, and nonexercise activity thermogenesis were not different between the elderly and young groups. Thus, the energetic cost of walking in the elderly may be greater than in the young. Lean, healthy elderly individuals may have a biological drive to be less active than the young.

scholarly journals The role of oxidant-antioxidant markers and resistin in metabolic syndrome elderly individuals

2021 ◽  
Vol 104 (2) ◽  
pp. 003685042110065
Author(s):  
Sylwia Dzięgielewska-Gęsiak ◽  
Karolina Wyszomirska ◽  
Edyta Fatyga ◽  
Ewa Wysocka ◽  
Małgorzata Muc-Wierzgoń
Keyword(s):  
Blood Pressure ◽  
Metabolic Syndrome ◽  
Diastolic Blood Pressure ◽  
Plasma Lipids ◽  
Fasting Glucose ◽  
The Elderly ◽  
Older Individuals ◽  
Elderly Individuals ◽  
Healthy Elderly ◽  
Antioxidant Markers

In elderly, hormones and oxidant-antioxidant interplay are suggested to mediate biochemical balance between adipose tissue to other tissues. Thus the study attempts to explore metabolic traits, plasma resistin, and oxidant-antioxidant markers in metabolic syndrome (MetS) in comparison to non-metabolic syndrome (non-MetS) elderly individuals. A total of 541 healthy elderly Caucasians, with no acute and/or chronic disorders were invited. After taking into account inclusion/exclusion criteria’s the MetS was defined as the presence of three out of five abnormal findings and allowed to divided groups into: non-metabolic syndrome, non-MetS ( n = 25, median age 69.0 years), and newly diagnosed MetS ( n = 29; median age 70.5 years) individuals. Glucose, plasma lipids, resistin (Res), thiobarbituric acid-reacting substances (TBARS), total antioxidant status (TAS), and Cu,Zn-superoxide dismutase (SOD-1) were measured. The MetS had higher resistin than non-MetS ( p < 0.04). The linear correlation (all at p < 0.05) showed correlation for Res&triacylglycerols ( R = 0.44), and for Res&diastolic blood pressure ( R = −0.58) and for SOD-1&fasting glucose ( R = −0.34) in MetS, while in the non-MetS group fasting glucose correlates with Res ( R = 0.58) and with TAS ( R = −0.43). The multiple regression analysis (alone and in combination) showed that independently from other factors resistin correlated positively with fasting glucose (β = 0.37; R = 0.58; R 2 = 0.23; p < 0.01) in all investigated elderly participants. In the MetS resistin correlated negatively with diastolic blood pressure (β = −0.68; R = 0.80; R 2 = 0.53; p = 0.0004) moreover in that group TAS correlated negatively with HDL-C (β = −0.71; R = 0.72; R 2 = 0.37; p = 0.01). While age correlated negatively with systolic blood pressure (β = −0.60; R = 0.62; R 2 = 0.14; p = 0.03) independently from other factors in the non-MetS group. Various metabolic factors contribute to maintain serum resistin and oxidant-antioxidant balance in the elderly people in the presence or absence of MetS. Resistin may serve as a predictor of MetS in the elderly, while strong antioxidant defense interactions in older individuals may indicate good health.

scholarly journals Compensatory effect of TNFalpha on low natural killer activity in the elderly.

2000 ◽  
Vol 47 (2) ◽  
pp. 301-311 ◽  
Author(s):  
J Myśliwska ◽  
E Bryl ◽  
P Trzonkowski ◽  
A Myśliwski
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Mononuclear Cells ◽  
Interleukin 2 ◽  
Natural Killer Activity ◽  
The Elderly ◽  
Nk Activity ◽  
Killer Activity ◽  
Healthy Elderly

Regulatory effect of CD25, an activation antigen the alpha subunit of interleukin 2 receptor (IL2R) on the activity of natural killer (NK) cells was studied in fifty elderly (57-70 years old) and fifty young people (19-35 years old). Cytotoxic NK activity was assessed by 51Cr release assay, the levels of interleukin 2 (IL2) and tumour necrosis factors alpha (TNFalpha) were measured using bioassays and expression of CD16 and CD25 proteins by flow cytometry. Low NK activity in the elderly was associated with decline of full health, lowered serum concentration of IL2 and increased production of TNFalpha during NK reaction. Inhibition of TNFalpha activity by anti-TNF monoclonal antibody suppressed exclusively NK activity of low NK responders. Moreover, stimulation in vitro of blood mononuclear cells, with TNFalpha induced in the elderly low NK responders a significantly higher increase of the CD25 expression on the surface of NK cells as compared with that in the elderly high responders. Since the CD25 molecule constitutes a subunit of the high affinity receptor, binding IL2 to immunocompetent cells, its increased expression on NK cells of low NK responders would enable them to bind even low amounts of the endogenous IL2 available in this group of the elderly. Thus, an overproduction of TNFalpha seems to be a mechanism compensating, in the non-fully healthy elderly, for the decreased IL2 production, promoting efficient cytotoxic reaction.

scholarly journals Dysregulation of TLR3 Impairs the Innate Immune Response to West Nile Virus in the Elderly

2008 ◽  
Vol 82 (15) ◽  
pp. 7613-7623 ◽  
Author(s):  
Kok-Fai Kong ◽  
Karine Delroux ◽  
Xiaomei Wang ◽  
Feng Qian ◽  
Alvaro Arjona ◽  
...  
Keyword(s):  
Immune Response ◽  
West Nile Virus ◽  
Innate Immune Response ◽  
The Elderly ◽  
Innate Immune ◽  
Intercellular Adhesion Molecule ◽  
Older Individuals ◽  
West Nile ◽  
Cytokine Levels

ABSTRACT West Nile virus (WNV), a mosquito-borne flavivirus, has recently emerged in North America, and the elderly are particularly susceptible to severe neurological disease and death from infection with this virus. We have investigated the innate immune response of primary human macrophages to WNV in vitro and have found significant differences between the responsiveness of macrophages derived from younger donors and that from older donors. Binding of the glycosylated WNV envelope protein to the C-type lectin dendritic cell-specific intercellular adhesion molecule 3 (ICAM3) grabbing nonintegrin (DC-SIGN) leads to a reduction in the expression of Toll-like receptor 3 (TLR3) in macrophages from young donors via the signal transducer and activator of transcription 1 (STAT1)-mediated pathway. This signaling is impaired in the elderly, and the elevated levels of TLR3 result in an elevation of cytokine levels. This alteration of the innate immune response with aging may contribute to the permeability of the blood-brain barrier and suggests a possible mechanism for the increased severity of WNV infection in older individuals.

scholarly journals Effects of dietaryn-3 polyunsaturated fatty acids from plant and marine origin on platelet aggregation in healthy elderly subjects

1999 ◽  
Vol 82 (3) ◽  
pp. 183-191 ◽  
Author(s):  
A. G. C. L Wensing ◽  
R. P. Mensink ◽  
G. Hornstra
Keyword(s):  
Oleic Acid ◽  
Platelet Aggregation ◽  
Linolenic Acid ◽  
Ex Vivo ◽  
Platelet Rich Plasma ◽  
The Elderly ◽  
Elderly Subjects ◽  
Healthy Elderly ◽  
Healthy Elderly Subjects

In the present intervention study we compared the effects of α-linolenic acid with those of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on platelet aggregationin vitroandex vivoin healthy non-institutionalized elderly subjects. We also compared the effects of α-linolenic acid on platelet aggregation in elderly subjects with those in younger volunteers. During a run-in period of 3 weeks all subjects (thirty-eight elderly (> 60 years) and twelve younger volunteers (< 35 years)) received a diet rich in oleic acid. For the next 6 weeks the elderly subjects received a diet rich in oleic acid (n11), α-linolenic acid (n14) (6·8 g/d) or EPA/DHA (n13) (1·05 g EPA plus 0·55 g DHA). The younger subjects were given a diet rich in α-linolenic acid. The diets did not affect ADP- or collagen-induced platelet aggregationin vitroin either platelet-rich plasma or whole blood. Theex vivoplatelet aggregation as measured with filtragometry was significantly decreased in the elderly group that received EPA/DHA compared with the α-linolenic acid (P= 0·006) and the oleic acid (P= 0·005) diet groups. Effects of α-linolenic acid were not age-dependent. Our results suggest that α-linolenic acid and EPA/DHA do not changein vitroplatelet aggregation. Compared with oleic acid, EPA/DHA, but not α-linolenic acid, favourably affectsex vivoplatelet aggregation in healthy elderly subjects.

Evidence for Associations Between Th1/Th17 “Hybrid” Phenotype and Altered Lipometabolism in Very Severe Graves Orbitopathy

2020 ◽  
Vol 105 (6) ◽  
pp. 1851-1867 ◽  
Author(s):  
Sijie Fang ◽  
Shuo Zhang ◽  
Yazhuo Huang ◽  
Yu Wu ◽  
Yi Lu ◽  
...  
Keyword(s):  
T Cell ◽  
Th17 Cell ◽  
Th17 Cells ◽  
T Cell Subsets ◽  
Th1 Cell ◽  
Effector T Cell ◽  
Cell Lineages ◽  
Graves Orbitopathy ◽  
Ifn Γ

Abstract Purpose The purpose of this article is to investigate the characteristics of Th1-cell and Th17-cell lineages for very severe Graves orbitopathy (GO) development. Methods Flow cytometry was performed with blood samples from GO and Graves disease (GD) patients and healthy controls, to explore effector T-cell phenotypes. Lipidomics was conducted with serum from very severe GO patients before and after glucocorticoid (GC) therapy. Immunohistochemistry and Western blotting were used to examine orbital-infiltrating Th17 cells or in vitro models of Th17 polarization. Results In GD, Th1 cells predominated in peripheral effector T-cell subsets, whereas in GO, Th17-cell lineage predominated. In moderate-to-severe GO, Th17.1 cells expressed retinoic acid receptor-related orphan receptor-γt (RORγt) independently and produced interleukin-17A (IL-17A), whereas in very severe GO, Th17.1 cells co-expressed RORγt and Tbet and produced interferon-γ (IFN-γ). Increased IFN-γ–producing Th17.1 cells positively correlated with GO activity and were associated with the development of very severe GO. Additionally, GC therapy inhibited both Th1-cell and Th17-cell lineages and modulated a lipid panel consisting of 79 serum metabolites. However, in GC-resistant, very severe GO, IFN-γ–producing Th17.1 cells remained at a high level, correlating with increased serum triglycerides. Further, retro-orbital tissues from GC-resistant, very severe GO were shown to be infiltrated by CXCR3+ Th17 cells expressing Tbet and STAT4 and rich in triglycerides that promoted Th1 phenotype in Th17 cells in vitro. Conclusions Our findings address the importance of Th17.1 cells in GO pathogenesis, possibly promoting our understanding of the association between Th17-cell plasticity and disease severity of GO.

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