Immunity & Ageing最新文献

{"title":"Disrupted mitochondrial morphology and function exacerbate inflammation in elderly-onset ulcerative colitis.","authors":"Mengmeng Zhang, Hong Lv, Xiaoyin Bai, Gechong Ruan, Qing Li, Kai Lin, Hong Yang, Jiaming Qian","doi":"10.1186/s12979-024-00494-5","DOIUrl":"10.1186/s12979-024-00494-5","url":null,"abstract":"<p><strong>Background: </strong>The characteristics of ulcerative colitis (UC) in the elderly are quite different from the young population. Mitochondrial injury is a key mechanism regulating both aging and inflammation. This study aims to reveal the role of mitochondrial damage in the pathogenesis of adult- and elderly-onset UC.</p><p><strong>Methods: </strong>RNA-sequencing of colonic mucosa from adult- and elderly-onset UC patients was performed. Mitochondria-related differentially expressive genes (mDEGs) and immune cell infiltration analysis were identified and performed in colonic tissues from UC patients. Mice aged 6-8 weeks and 20-24 months were administered 2% dextran sodium sulphate (DSS) for 7 days to induce colitis. Mitochondrial morphological changes and ATP levels were evaluated in the colons of mice. Mechanistically, we explored the association of key mDEG with reactive oxygen species (ROS), oxygen consumption rates, NLRP3/IL-1β pathway in HCT116 cell line.</p><p><strong>Results: </strong>Thirty mDEGs were identified between adult- and elderly-onset UC, which were related primarily to mitochondrial respiratory function and also had significant correlation with different infiltrates of immune cells. Compared with young colitis mice, DSS-induced colitis in the aged mice exhibited more severe inflammation, damaged mitochondrial structure and lower ATP levels in colonic tissues. ALDH1L1 was identified as a hub DEG through protein-protein interaction networks of RNA-seq, which was downregulated in UC patients or colitis mice versus healthy controls. In tumor necrosis factor-alpha-stimulated HCT116 cells, mitochondrial ROS, NLRP3 and IL-1β expression increased less and mitochondrial respiration had an upregulated trend after knocking down ALDH1L1.</p><p><strong>Conclusion: </strong>There are significant differences in mitochondrial structure, ATP production and mitochondria-related gene expression between adult- and elderly-onset UC, which have a potential link with cytokine pathways and immune microenvironment. The more prominent mitochondrial injury may be a key factor for more severe inflammatory response and poorer outcome in elderly-onset UC.</p>","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":"22 1","pages":"4"},"PeriodicalIF":5.2,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11721460/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142967333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Limited restoration of T cell subset distribution and immune function in older people living with HIV-1 receiving HAART.","authors":"Na Li, Hong-Yi Zheng, Wei Li, Xiao-Yan He, Mi Zhang, Xia Li, Ren-Rong Tian, Xing-Qi Dong, Zhi-Qiang Shen, Yong-Tang Zheng","doi":"10.1186/s12979-024-00497-2","DOIUrl":"10.1186/s12979-024-00497-2","url":null,"abstract":"<p><strong>Background: </strong>Older people living with HIV-1 (PLWH) experience a dual burden from the combined effects of aging and HIV-1 infection, resulting in significant immune dysfunction. Despite receiving HAART, immune reconstitution is not fully optimized. The objective of this study was to investigate the impact of aging and HAART on T cell subsets and function in PLWH across different age groups, thereby providing novel insights into the prognosis of older PLWH.</p><p><strong>Method: </strong>This study was conducted at Yunnan AIDS Care Center, China, to explore the immunological responses of old PLWH to HAART and compared with the middle-age and the younger. Blood samples were collected from 146 PLWH to analyze T cell subsets and their functions, with a particular emphasis on markers related to T cell differentiation, activation, exhaustion, inflammation, and cellular function, using multicolor flow cytometry analysis.</p><p><strong>Results: </strong>Older age may have a greater effect on long-term CD4⁺T cell recovery. Compared with young and middle-aged PLWH, older PLWH presented distinct alterations in their immune profile, including a decline in the Naïve CD4⁺T and CD8⁺T cell subsets, an expansion of effector memory cells, and other potential immune risk phenotypes, such as activation, exhaustion, and up-regulation of aging markers. In addition, we observed a significant association between the CD4 + EM3 subset and the CD8 + EM2 subset with HIV-1 progression, independent of age, suggesting their potential as reliable markers for assessing immune reconstitution in all PLWH.</p><p><strong>Conclusion: </strong>Our study extends previous findings showing that older participants exhibit a wide range of late differentiation, senescence, or exhaustion phenotypes in cells, including all the CD4⁺T and CD8⁺T subsets, consistent with an immunosenescent phenotype. This may accelerate poor immune recovery in older PLWH. Identifying new strategies to improve the immune risk phenotypes of older PLWH may help improve their immune reconstitution outcomes. The CD4 + EM3 subset and the CD8 + EM2 subset should be studied as additional markers of late presentation.</p>","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":"22 1","pages":"3"},"PeriodicalIF":5.2,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11708165/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142958467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Obesity-associated memory impairment and neuroinflammation precede widespread peripheral perturbations in aged rats.","authors":"Michael J Butler, Stephanie M Muscat, Maria Elisa Caetano-Silva, Akriti Shrestha, Brigitte M González Olmo, Sabrina E Mackey-Alfonso, Nashali Massa, Bryan D Alvarez, Jade A Blackwell, Menaz N Bettes, James W DeMarsh, Robert H McCusker, Jacob M Allen, Ruth M Barrientos","doi":"10.1186/s12979-024-00496-3","DOIUrl":"10.1186/s12979-024-00496-3","url":null,"abstract":"<p><strong>Background: </strong>Obesity and metabolic syndrome are major public health concerns linked to cognitive decline with aging. Prior work from our lab has demonstrated that short-term high fat diet (HFD) rapidly impairs memory function via a neuroinflammatory mechanism. However, the degree to which these rapid inflammatory changes are unique to the brain is unknown. Moreover, deviations in gut microbiome composition have been associated with obesity and cognitive impairment, but how diet and aging interact to impact the gut microbiome, or how rapidly these changes occur, is less clear. Thus, our study investigated the impact of HFD after two distinct consumption durations: 3 months (to model diet-induced obesity) or 3 days (to detect the rapid changes occurring with HFD) on memory function, anxiety-like behavior, central and peripheral inflammation, and gut microbiome profile in young and aged rats.</p><p><strong>Results: </strong>Our data indicated that both short-term and long-term HFD consumption impaired memory function and increased anxiety-like behavior in aged, but not young adult, rats. These behavioral changes were accompanied by pro- and anti-inflammatory cytokine dysregulation in the hippocampus and amygdala of aged HFD-fed rats at both time points. However, changes to fasting glucose, insulin, and inflammation in peripheral tissues such as the distal colon and visceral adipose tissue were increased in young and aged rats only after long-term, but not short-term, HFD consumption. Furthermore, while subtle HFD-induced changes to the gut microbiome did occur rapidly, robust age-specific effects were only present following long-term HFD consumption.</p><p><strong>Conclusions: </strong>Overall, these data suggest that HFD-evoked neuroinflammation, memory impairment, and anxiety-like behavior in aging develop quicker than, and separately from the peripheral hallmarks of diet-induced obesity.</p>","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":"22 1","pages":"2"},"PeriodicalIF":5.2,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11697663/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142928499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High SARS-CoV-2 antibody levels after three consecutive BNT162b2 booster vaccine doses in nursing home residents.","authors":"Marloes I Hofstee, Joanna Kaczorowska, Abigail Postema, Erna Zomer, Maren van Waalwijk, Gustaaf Jonathans, Lia Gh de Rond, Gaby Smits, Lotus L van den Hoogen, Gerco den Hartog, Anne-Marie Buisman","doi":"10.1186/s12979-024-00495-4","DOIUrl":"10.1186/s12979-024-00495-4","url":null,"abstract":"<p><strong>Background: </strong>As older age and having certain comorbidities can influence humoral responses to vaccination, we studied antibody responses after the COVID-19 booster campaigns in nursing home (NH) residents.</p><p><strong>Methods: </strong>In a two year longitudinal study with Dutch NH residents (n = 107), aged 50 years and over, we monitored antibody responses in serum prior to and after vaccination with a third, fourth BNT162b2 (wild-type; WT), and a BNT162b2 bivalent (WT/OMI BA.1) fifth vaccine. Data on vaccinations, infections, comorbidities, and, for some participants, clinical symptoms after infection were obtained with questionnaires. Data were compared to antibody responses of BNT162b2-vaccinated, healthier community-dwelling older adults (n = 32) from the general population.</p><p><strong>Results: </strong>The booster vaccinations substantially increased anti-WT and anti-Omicron SARS-CoV-2 Spike S1 (S1) and Spike protein receptor binding domain (RBD)-antibody concentrations of NH residents. This resulted in comparable antibody levels between NH residents and healthier community-dwelling older adults and between infection-naïve and infected NH residents, and in a decline in treatment duration and clinical symptom severity in SARS-CoV-2-infected NH residents. Between one and twelve months after the bivalent fifth dose, anti-Omicron BA.1 antibody levels of the NH residents waned faster than those against the WT strain.</p><p><strong>Conclusions: </strong>The booster vaccinations upheld humoral responses of NH residents to WT and Omicron SARS-CoV-2. This, in addition to the less virulent circulating strains, decreased symptom severity and treatment durations for SARS-CoV-2-infected NH residents. Boosting this vulnerable group should, therefore, be continued to prevent waning of humoral immunity and achieve sufficient protection especially against newly emerging variants of concern.</p>","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":"22 1","pages":"1"},"PeriodicalIF":5.2,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11694371/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142924027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"scRNA + BCR-seq identifies proportions and characteristics of dual BCR B cells in the peritoneal cavity of mice and peripheral blood of healthy human donors across different ages.","authors":"Huifang Wang, Jun Li, Yuanyuan Xu, Xinsheng Yao","doi":"10.1186/s12979-024-00493-6","DOIUrl":"10.1186/s12979-024-00493-6","url":null,"abstract":"<p><p>The increased incidence of inflammatory diseases, infectious diseases, autoimmune disorders, and tumors in elderly individuals is closely associated with several well-established features of immunosenescence, including reduced B cell genesis and dampened immune responses. Recent studies have highlighted the critical role of dual receptor lymphocytes in tumors and autoimmune diseases. This study utilized shared data generated through scRNA-seq + scBCR-seq technology to investigate the presence of dual receptor-expressing B cells in the peritoneum of mouse and peripheral blood of healthy volunteers, and whether there are age-related differences in dual receptor B cell populations. In the peritoneum of mice, a high proportion of B cells expressing dual receptors, predominantly dual κ chains, was observed. Notably, there was an increase in dual BCR B cells in elderly mice. Subsequent analysis revealed that the elevated dual BCR B cells in elderly mice primarily originated from B1 cells.Consistent with the results we observed in healthy volunteers of different ages. Furthermore, these cells exhibited differential expressed genes compared to single BCR B cells, including Vim, Ucp2, and Zcwpw1.These findings support a hypothesis that age-related immune changes encompass not only alterations in B cell numbers but also qualitative changes in BCR diversity. Further exploration of the elevated dual BCR B cells in the elderly population can elucidate their function and their association with immune tolerance, revealing their potential role in maintaining immune surveillance and responding to age-related immune challenges.</p>","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":"21 1","pages":"90"},"PeriodicalIF":5.2,"publicationDate":"2024-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11681687/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142900329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CD57⁺ EMRA CD8⁺ T cells in cancer patients over 70: associations with prior chemotherapy and response to anti-PD-1/PD-L1 therapy.","authors":"Cécile Gonnin, Michelle Leemans, Florence Canoui-Poitrine, Morgane Lebraud, Aurélien Corneau, Louise Roquebert, Philippe Caillet, Pierre Gay, Johanna Canovas, Axelle Histe, Catherine Blanc, Carine El-Sissy, Anis Larbi, Johanne Poisson, Pauline Ober, Pascaline Boudou-Rouquette, Pierre-André Natella, Hélène Vallet, Besma Saadaoui, Richard Layese, Eric Tartour, Elena Paillaud, Clémence Granier","doi":"10.1186/s12979-024-00487-4","DOIUrl":"10.1186/s12979-024-00487-4","url":null,"abstract":"<p><strong>Background: </strong>Immune ageing complicates cancer treatment in older individuals. While immunotherapy targeting the PD-1/PD-L1 pathway can reinvigorate T cells, these cells tend to become senescent with age. This study investigates different CD8⁺ T cell subsets usually associated with senescence, in cancer patients over 70 years old who are undergoing anti-PD-1/PD-L1 immunotherapy, and examines the relationship between these senescent cells and prior chemotherapy exposure. We analyzed data from the Elderly Cancer Patient (ELCAPA) cohort, which included 35 patients enrolled between March 2018 and March 2021.</p><p><strong>Results: </strong>Flow cytometry and unsupervised analysis were employed to characterize Effector Memory CD45RA⁺ (EMRA) and CD8⁺ T cell senescence at baseline, before initiating PD-1/PD-L1 therapy. EMRA cells were found to overexpress CD57 and KLRG1 compared to overall CD8⁺ T cells. Chemotherapy prior to anti-PD-1/PD-L1 was associated with an increased proportion of CD57⁺ EMRA CD8⁺ T cells (p = 0.009) and its granzyme B (GRZB) subset (p = 0.007). Using a 10% cut-off to define positivity, the six-month non-response tends to be associated with the CD57⁺ GRZB⁺ EMRA positivity (p = 0.097). Other CD8⁺ T cell subsets (EMRA, CD57⁺, or KLRG1⁺), usually associated with senescence, showed no significant association with previous chemotherapy or response to anti-PD-1/anti-PD-L1 therapy.</p><p><strong>Conclusions: </strong>These findings underscore the impact of prior chemotherapy on expanding the pool of senescent T cells, particularly CD57⁺ EMRA CD8⁺ T and CD57⁺ GRZB⁺ EMRA CD8⁺ T cells, whose expansion could potentially affect the effectiveness of anti-PD-1/PD-L1 immunotherapy in elderly patients. This highlights the need for tailored approaches in this population.</p>","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":"21 1","pages":"89"},"PeriodicalIF":5.2,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11673364/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142900318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Micro nutrients as immunomodulators in the ageing population: a focus on inflammation and autoimmunity.","authors":"Bhavani Sowndharya Balamurugan, Mathan Muthu Chinnakannu Marimuthu, Vickram Agaram Sundaram, Bharath Saravanan, Prasanth Chandrababu, Hitesh Chopra, Tabarak Malik","doi":"10.1186/s12979-024-00492-7","DOIUrl":"10.1186/s12979-024-00492-7","url":null,"abstract":"<p><p>Immunosenescence, the slow degradation of immune function over time that is a hallmark and driver of aging, makes older people much more likely to be killed by common infections (such as flu) than young adults, but it also contributes greatly to rates of chronic inflammation in later life. Such micro nutrients are crucial for modulating effective immune responses and their deficiencies have been associated with dysfunctional immunity in the elderly. In this review, we specifically focused on the contribution of major micro nutrients (Vitamins A, D and E, Vitamin C; Zinc and Selenium) as immunomodulators in ageing population especially related to inflame-ageing process including autoimmunity. This review will cover these hologenomic interactions, including how micro nutrients can modulate immune cell function and/or cytokine production to benefit their hosts with healthy mucous-associated immunity along with a sustainable immunologic homeostasis. For example, it points out the modulatory effects of vitamin D on both innate and adaptive immunity, with a specific focus on its ability to suppress pro-inflammatory cytokines synthesis while enhancing regulatory T-cell function. In the same context, also zinc is described as important nutrient for thymic function and T-cell differentiation but exhibits immunomodulatory functions by decreasing inflammation. In addition, the review will go over how micro nutrient deficiencies increase systemic chronic low-grade inflammation and, inflammaging as well as actually enhance autoimmune pathologies in old age. It assesses the potential role of additional targeted nutritional supplementation with micro nutrients to counteract these effects, promoting wider immune resilience in older adults. This review collates the current evidence and highlights the role of adequate micro nutrient intake on inflammation and autoimmunity during ageing, providing plausible origins for nutritional interventions to promote healthy immune aging.</p>","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":"21 1","pages":"88"},"PeriodicalIF":5.2,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11674512/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142900327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential associations of anti-cytomegalovirus antibodies and soluble CD14 levels with immunosenescence in people living with HIV on long term antiretroviral therapy.","authors":"Ashwini Vinod Shete, Pallavi Shidhaye, Amrita Rao, Nikita Bhawari, Supriya Deshpande, Jyoti Sawant, Rajani Bagul, Ujjwala Ghule, Sunita Kumbhar, Manisha Ghate","doi":"10.1186/s12979-024-00491-8","DOIUrl":"10.1186/s12979-024-00491-8","url":null,"abstract":"<p><strong>Background: </strong>People living with HIV (PLHIV) demonstrate accelerated aging and immunosenescence in spite of immune-restoration following long-term antiretroviral treatment (ART). Low level inflammation leading to inflammaging plays an important role in mediating premature immunosenescence. Ongoing viral replication, antiretrovirals and subclinical infections with the common viruses like Cytomegalovirus (CMV) are known to induce inflammaging. However such data is scarce in India where persistent low level inflammation is common in general population due to various subclinical infections. Hence we conducted a study to determine the extent of immunosenescence in asymptomatic PLHIV on long term ART in comparison with their age-matched controls.</p><p><strong>Results: </strong>The study was conducted in asymptomatic virally suppressed PLHIV on ART for more than 5 years [n = 70, M: F = 36:34] and HIV uninfected controls [n = 68, M: F = 31:37] belonging to the age-group of 40-55 years. Blood samples were collected for assessing levels of immunosenescence markers on CD4 T cells by flow cytometry and anti-CMV antibodies as well as soluble CD14 (sCD14) levels by ELISA. The levels were compared between cases and controls and correlated with the levels of anti-CMV antibody and sCD14. PLHIV had significantly lower levels of naïve T cells and higher levels of activated and immunosenescent T cells than controls as indicated by CD38, CD57, CD28 expressing CD4 and CD8 T cells. PLHIV had higher levels of anti-CMV antibodies, but lower levels of sCD14 levels and HLADR + CD8 T cells than those in controls. Immunosenescent T cells correlated positively with anti-CMV antibody levels and negatively with sCD14 levels. Duration of dolutegravir based therapy correlated negatively with sCD14 levels.</p><p><strong>Conclusions: </strong>Thus, higher levels of immune activation and immunosenescence in the cases possibly indicate their compromised immune status predisposing PLHIV to infections and cancers. The study indicated a need for CMV treatment regimens even in asymptomatic individuals for preventing immunosenescence. The study also indicated a role of dolutegravir induced loss of sCD14 levels in predisposing PLHIV to immunosenescence.</p>","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":"21 1","pages":"87"},"PeriodicalIF":5.2,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11662588/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142873518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterisation of specific responses to three models of viral antigens in immunocompetent older adults.","authors":"Beatriz Rioseras, Eva Bueno-García, Alejandra García-Torre, Rocío López-Martínez, Marco Antonio Moro-García, Sara Alonso-Álvarez, Victoria Menéndez-García, Alba Lluna-González, Alejandra Sousa-Fernández, Marta Fernández-Gudin, Laura Campos-Riopedre, Corina Castro-Del Cueto, Ana Belén Pérez-Fernández, Ana Alonso-Rodríguez, Carla Menéndez-Peña, Lara Menéndez-Peña, Noelia García-Arnaldo, Estefanía Feito-Díaz, Adriana Fernández-Lorences, Agustín Fraile-Manzano, Carolina Fernández-Iglesias, Jose Arturo Rivera, Carmen Pérez-Fonseca, Estíbaliz Urdiales-Ruano, María Debán-Fernández, Hugo Mendes-Moreira, Pablo Herrero-Puente, Rebeca Alonso-Arias","doi":"10.1186/s12979-024-00488-3","DOIUrl":"10.1186/s12979-024-00488-3","url":null,"abstract":"<p><strong>Background: </strong>Memory responses to the antigens that an individual encounters throughout life may vary with the intensity and duration of antigen contacts or even with changes in immune status over time. This work aims to characterise specific responses to latent CMV, seasonal influenza and novel SARS-CoV-2 infections in immunocompetent individuals over 60 years of age. Specific cellular and humoral responses were identified by IFN-γ and granzyme B release by ELISpot and antibody level measurement. T lymphocyte subpopulation phenotypes were characterised by flow cytometry.</p><p><strong>Results: </strong>Cellular and humoral responses to these viruses were detected in almost all patients. Influenza and SARS-CoV-2 cellular responses were positively correlated. There was no significant correlation between CMV and influenza or SARS-CoV-2 responses although both were consistently lower in CMV-seropositive patients. CMV responses were negatively correlated with the levels of the least differentiated subsets of T lymphocytes, and positively correlated with the most differentiated ones, contrary to what happened with the influenza responses. Nevertheless, SARS-CoV-2 cellular responses were negatively correlated with the most differentiated CD8⁺ T lymphocytes, while humoral responses were negatively correlated with the least differentiated T lymphocytes. Responses to the three viruses were correlated with a Th1/Th2/Th17 balance in favour of Th1.</p><p><strong>Conclusions: </strong>The results indicate that memory responses differ depending on the durability of the antigen stimulus. Cellular responses to novel pathogens resemble those generated by seasonal but not CMV infection. Subpopulation distribution and the level of specific T lymphocytes against previous pathogens could be used as immunocompetent status biomarkers in older adults reflecting their ability to generate memory responses to new pathogens.</p>","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":"21 1","pages":"86"},"PeriodicalIF":5.2,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11619616/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142787531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of autoantibodies in bridging obesity, aging, and immunosenescence.","authors":"Taylor R Valentino, Nan Chen, Priya Makhijani, Saad Khan, Shawn Winer, Xavier S Revelo, Daniel A Winer","doi":"10.1186/s12979-024-00489-2","DOIUrl":"https://doi.org/10.1186/s12979-024-00489-2","url":null,"abstract":"<p><p>Antibodies are essential to immune homeostasis due to their roles in neutralizing pathogenic agents. However, failures in central and peripheral checkpoints that eliminate autoreactive B cells can undermine self-tolerance and generate autoantibodies that mistakenly target self-antigens, leading to inflammation and autoimmune diseases. While autoantibodies are well-studied in autoimmune and in some communicable diseases, their roles in chronic conditions, such as obesity and aging, are less understood. Obesity and aging share similar aspects of immune dysfunction, such as diminished humoral responses and heightened chronic inflammation, which can disrupt immune tolerance and foster autoantigen production, thus giving rise to autoreactive B cells and autoantibodies. In return, these events may also contribute to the pathophysiology of obesity and aging, to the associated autoimmune disorders linked to these conditions, and to the development of immunosenescence, an age-related decline in immune function that heightens vulnerability to infections, chronic diseases, and loss of self-tolerance. Furthermore, the cumulative exposure to antigens and cellular debris during obesity and aging perpetuates pro-inflammatory pathways, linking immunosenescence with other aging hallmarks, such as proteostasis loss and mitochondrial dysfunction. This review examines the mechanisms driving autoantibody generation during obesity and aging and discusses key putative antigenic targets across these conditions. We also explore the therapeutic potential of emerging approaches, such as CAR-T/CAAR-T therapies, vaccines, and BiTEs, to tackle autoimmune-related conditions in aging and obesity.</p>","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":"21 1","pages":"85"},"PeriodicalIF":5.2,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11607830/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142774310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}