Human Monocyte Subsets Are Transcriptionally and Functionally Altered in Aging in Response to Pattern Recognition Receptor Agonists
Open accessAbstract
Age-related alterations in immunity have been linked to increased incidence of infections and decreased responses to vaccines in the aging population. Human peripheral blood monocytes are known to promote Ag presentation and antiviral activities; however, the impact of aging on monocyte functions remains an open question. We present an in-depth global analysis examining the impact of aging on classical (CD14+CD16−), intermediate (CD14+CD16+), and nonclassical (CD14dimCD16+) monocytes. Monocytes sorted from nonfrail healthy adults (21–40 y) and old (≥65 y) individuals were analyzed after stimulation with TLR4, TLR7/8, and retinoic acid–inducible gene I agonists. Our data showed that under nonstimulated conditions, monocyte subsets did not reveal significant age-related alternations; however, agonist stimulated-monocytes from adults and old subjects did show differences at the transcriptional and functional levels. These alternations in many immune-related transcripts and biological processes resulted in reduced production of IFN-α, IFN-γ, IL-1β, CCL20, and CCL8, and higher expression of CX3CR1 in monocytes from old subjects. Our findings represent a comprehensive analysis of the influence of human aging on pattern recognition receptors signaling and monocyte functions, and have implications for strategies to enhance the immune response in the context of infection and immunization.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Many immune cell subsets become hyporesponsive to acute challenges with age.
“Thus, many immune cell subsets become hyporesponsive to acute challenges as we age17,19-25.”
From SARS-CoV-2, COVID-19 and the aging immune system (2021) · cites this paper as [23]
In a study by Metcalf et al, the three monocyte populations were isolated and examined separately, and baseline monocytes from young and old donors were found to be similar.
“isolated the three monocyte populations and studied them individually, showing that at baseline, monocytes from young and old people were similar.”
From The impact of ageing on monocytes and macrophages (2021) · cites this paper as [137]
After stimulation with TLR4, TLR7/8 and RIG-I, monocytes from older people produced lower amounts of pro-inflammatory cytokines, including IL-1β and IFNα, than those from young people.
“upon stimulation with TLR4, TLR7/8 and retinoic acid-inducible gene I (RIG-I), aged monocytes produced less pro-inflammatory cytokines, such as IL-1β and IFNα (137).”
From The impact of ageing on monocytes and macrophages (2021) · cites this paper as [137]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
R: A Language and Environment for Statistical Computing
R Core Team (2000) · doi:10.32614/r.manuals · Cited by 355,706 · see citing works
Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing
Benjamini, Y., & Hochberg, Y. (1995) · Journal of the Royal Statistical Society Series B: Statistical Methodology · doi:10.1111/j.2517-6161.1995.tb02031.x · Cited by 109,482 · see citing works
Subramanian, A., Tamayo, P., Mootha, V. K., Mukherjee, S., Ebert, B. L., Gillette, M. A., Paulovich, A., Pomeroy, S. L., Golub, T. R., Lander, E. S., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506580102 · Cited by 53,625 · see citing works
limma powers differential expression analyses for RNA-sequencing and microarray studies
Ritchie, M. E., Phipson, B., Wu, D., Hu, Y., Law, C. W., Shi, W., & Smyth, G. K. (2015) · Nucleic Acids Research · doi:10.1093/nar/gkv007 · Cited by 40,458 · see citing works
Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources
Huang, D. W., Sherman, B. T., & Lempicki, R. A. (2009) · Nature Protocols · doi:10.1038/nprot.2008.211 · Cited by 35,890 · see citing works
GSVA: gene set variation analysis for microarray and RNA-Seq data
Hänzelmann, S., Castelo, R., & Guinney, J. (2013) · BMC Bioinformatics · doi:10.1186/1471-2105-14-7 · Cited by 15,440 · see citing works
Huang, D. W., Sherman, B. T., & Lempicki, R. A. (2009) · Nucleic Acids Research · doi:10.1093/nar/gkn923 · Cited by 14,108 · see citing works
Bioconductor: open software development for computational biology and bioinformatics
Gentleman, R., Carey, V., Bates, D., Bolstad, B., Dettling, M., Dudoit, S., Ellis, B., Gautier, L., Ge, Y., Gentry, J., et al. (2004) · Genome Biology · doi:10.1186/gb-2004-5-10-r80 · Cited by 13,133 · see citing works
limma: Linear Models for Microarray Data
Smyth, G. K. (2005) · Statistics for Biology and Health · doi:10.1007/0-387-29362-0_23 · Cited by 5,796 · see citing works
Progress in Development of the Index of ADL
Katz, S., Downs, T. D., Cash, H., & Grotz, R. C. (1970) · The Gerontologist · doi:10.1093/geront/10.1_part_1.20 · Cited by 4,129 · see citing works
Immunological and inflammatory functions of the interleukin-1 family
Dinarello, C. A. (2009) · Annual Review of Immunology · doi:10.1146/annurev.immunol.021908.132612 · Cited by 3,466 · see citing works
Franceschi, C., Capri, M., Monti, D., Giunta, S., Olivieri, F., Sevini, F., Panourgia, M. P., Invidia, L., Celani, L., Scurti, M., et al. (2007) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2006.11.016 · Cited by 2,087 · see citing works
From Monocytes to M1/M2 Macrophages: Phenotypical vs. Functional Differentiation
Italiani, P., & Boraschi, D. (2014) · Frontiers in Immunology · doi:10.3389/fimmu.2014.00514 · Cited by 2,067 · see citing works
Antimicrobial reactive oxygen and nitrogen species: concepts and controversies
Fang, F. C. (2004) · Nature Reviews Microbiology · doi:10.1038/nrmicro1004 · Cited by 1,676 · see citing works
The Mini-Cog as a screen for dementia: validation in a population-based sample
Borson, S., Scanlan, J. M., Chen, P., & Ganguli, M. (2003) · Journal of the American Geriatrics Society · doi:10.1046/j.1532-5415.2003.51465.x · Cited by 1,348 · see citing works
Human CD14dim Monocytes Patrol and Sense Nucleic Acids and Viruses via TLR7 and TLR8 Receptors
Cros, J. F., Cagnard, N., Woollard, K. J., Patey, N., Zhang, S., Sénéchal, B., Puel, A., Biswas, S. K., Moshous, D., Pïcard, C., et al. (2010) · Immunity · doi:10.1016/j.immuni.2010.08.012 · Cited by 1,251 · see citing works
Lymphocyte traffic control by chemokines
Moser, B., & Loetscher, P. (2001) · Nature Immunology · doi:10.1038/84219 · Cited by 1,235 · see citing works
Monocyte-Mediated Defense Against Microbial Pathogens
Serbina, N. V., Jia, T., Hohl, T. M., & Pamer, E. G. (2008) · Annual Review of Immunology · doi:10.1146/annurev.immunol.26.021607.090326 · Cited by 1,116 · see citing works
Wong, K. L., Tai, J. J.-Y., Wong, W. C., Han, H., Sem, X., Yeap, W., Kourilsky, P., & Wong, S. C. (2011) · Blood · doi:10.1182/blood-2010-12-326355 · Cited by 1,111 · see citing works
The CD14+ CD16+ blood monocytes: their role in infection and inflammation
Ziegler‐Heitbrock, L. (2006) · Journal of Leukocyte Biology · doi:10.1189/jlb.0806510 · Cited by 1,045 · see citing works
Gavazzi, G., & Krause, K.-H. (2002) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(02)00437-1 · Cited by 990 · see citing works
Reactive oxygen species and cell signaling: Respiratory burst in macrophage signaling
Forman, H. J., & Torres, M. (2002) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.2206007 · Cited by 891 · see citing works
The Proinflammatory CD14+CD16+DR++ Monocytes Are a Major Source of TNF
Belge, K.-U., Dayyani, F., Horelt, A., Siedlar, M., Frankenberger, M., Frankenberger, B., Espevik, T., & Ziegler-Heitbrock, L. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.168.7.3536 · Cited by 883 · see citing works
Human Monocytes Engage an Alternative Inflammasome Pathway
Gaidt, M. M., Ebert, T. S., Chauhan, D., Schmidt, T., Schmid-Burgk, J. L., Rapino, F. A., Robertson, A. A. B., Cooper, M. A., Graf, T., & Hornung, V. (2016) · Immunity · doi:10.1016/j.immuni.2016.01.012 · Cited by 780 · see citing works
The CC chemokine CCL20 and its receptor CCR6
Schutyser, E., Struyf, S., & Damme, J. V. (2003) · Cytokine & Growth Factor Reviews · doi:10.1016/s1359-6101(03)00049-2 · Cited by 777 · see citing works
Jakubzick, C. V., Gautier, E., Gibbings, S. L., Sojka, D. K., Schlitzer, A., Johnson, T. E., Ivanov, S., Duan, Q., Bala, S., Condon, T., et al. (2013) · Immunity · doi:10.1016/j.immuni.2013.08.007 · Cited by 762 · see citing works
Yellow fever vaccine induces integrated multilineage and polyfunctional immune responses
Gaucher, D., Therrien, R., Kettaf, N., Angermann, B., Boucher, G., Filali-Mouhim, A., Moser, J. M., Mehta, R. S., Drake, D. R., Castro, E., et al. (2008) · The Journal of Experimental Medicine · doi:10.1084/jem.20082292 · Cited by 589 · see citing works
Self-citationFractalkine Preferentially Mediates Arrest and Migration of CD16+ Monocytes
Ancuța, P., Rao, R., Moses, A. V., Mehle, A., Shaw, S. K., Luscinskas, F. W., & Gabuzda, D. H. (2003) · The Journal of Experimental Medicine · doi:10.1084/jem.20022156 · Cited by 566 · see citing works
SuperSAGE evidence for CD14++CD16+ monocytes as a third monocyte subset
Zawada, A. M., Rogacev, K. S., Rotter, B., Winter, P., Marell, R.-R., Fliser, D., & Heine, G. H. (2011) · Blood · doi:10.1182/blood-2011-01-326827 · Cited by 562 · see citing works
Measures of frailty in population-based studies: an overview
Bouillon, K., Mika Kivimaki, B., Hamer, M., Sabia, S., Fransson, E. I., Singh‐Manoux, A., Galé, C. R., & Batty, G. D. (2013) · BMC Geriatrics · doi:10.1186/1471-2318-13-64 · Cited by 466 · see citing works
Geissmann, F., Auffray, C., Palframan, R. T., Wirrig, C., Ciocca, A., Campisi, L., Narni-Mancinelli, É., & Lauvau, G. S. (2008) · Immunology and Cell Biology · doi:10.1038/icb.2008.19 · Cited by 385 · see citing works
Immunosenescence: Implications for response to infection and vaccination in older people
Pera, A., Campos, C., López, N., Hassouneh, F., Alonso, C., Tarazona, R., & Solana, R. (2015) · Maturitas · doi:10.1016/j.maturitas.2015.05.004 · Cited by 373 · see citing works
Redox control of senescence and age-related disease.
Chandrasekaran, A., Idelchik, M. D. P. S., & Melendez, J. A. (2017) · Redox Biology · doi:10.1016/j.redox.2016.11.005 · Cited by 360 · see citing works
Monocyte trafficking in acute and chronic inflammation
Ingersoll, M. A., Platt, A. M., Potteaux, S., & Randolph, G. J. (2011) · Trends in Immunology · doi:10.1016/j.it.2011.05.001 · Cited by 348 · see citing works
Ancuța, P., Liu, K., Misra, V., Wacleche, V. S., Gosselin, A., Zhou, X., & Gabuzda, D. H. (2009) · BMC Genomics · doi:10.1186/1471-2164-10-403 · Cited by 278 · see citing works
Snodgrass, R. G., Huang, S., Choi, I.-W., Rutledge, J. C., & Hwang, D. H. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1300298 · Cited by 243 · see citing works
Mx1 reveals innate pathways to antiviral resistance and lethal influenza disease
Pillai, P. S., Molony, R. D., Martinod, K., Dong, H., Pang, I. K., Tal, M. C., Solis, A. G., Bielecki, P., Mohanty, S., Trentalange, M. J., et al. (2016) · Science · doi:10.1126/science.aaf3926 · Cited by 241 · see citing works
Metcalf, T. U., Cubas, R. A., Ghneim, K., Cartwright, M. J., Grevenynghe, J. V., Richner, J. M., Olagnier, D. P., Wilkinson, P. A., Cameron, M. J., Park, B. S., et al. (2015) · Aging Cell · doi:10.1111/acel.12320 · Cited by 189 · see citing works
Self-citationTranscription and enhancer profiling in human monocyte subsets
Schmidl, C., Renner, K., Peter, K., Eder, R., Lassmann, T., Balwierz, P. J., Itoh, M., Nagao-Sato, S., Kawaji, H., Carninci, P., et al. (2014) · Blood · doi:10.1182/blood-2013-02-484188 · Cited by 170 · see citing works
Phenotypic and functional characteristics of circulating monocytes of elderly persons☆
Sadeghi, H. M., Schnelle, J. F., Thomas, J. K., Nishanian, P., & Fahey, J. L. (1999) · Experimental Gerontology · doi:10.1016/s0531-5565(99)00065-0 · Cited by 146 · see citing works
Extracellular activities of human granzyme A. Monocyte activation by granzyme A versus α-thrombin
Sower, L. E., Froelich, C. J., Allegretto, N. J., Rose, P. M., Hanna, W. D., & Klimpel, G. R. (1996) · The Journal of Immunology · doi:10.4049/jimmunol.156.7.2585 · Cited by 114 · see citing works
Distinct responses of monocytes to Toll-like receptor ligands and inflammatory cytokines
Farina, C. (2004) · International Immunology · doi:10.1093/intimm/dxh083 · Cited by 112 · see citing works
Katz, J. M., Plowden, J., Renshaw‐Hoelscher, M., Lu, X., Tumpey, T. M., & Sambhara, S. R. (2004) · Immunologic Research · doi:10.1385/ir:29:1-3:113 · Cited by 88 · see citing works
Ruffing, N., Sullivan, N. J., Sharmeen, L., Sodroski, J., & Wu, L. (1998) · Cellular Immunology · doi:10.1006/cimm.1998.1379 · Cited by 85 · see citing works
Human monocytes produce interferon-gamma upon stimulation with LPS
Kraaij, M. D., Vereyken, E. J. F., Leenen, P. J. M., van den Bosch, T. P. P., Rezaee, F., Betjes, M. G. H., Baan, C. C., & Rowshani, A. T. (2014) · Cytokine · doi:10.1016/j.cyto.2014.02.001 · Cited by 71 · see citing works
Non‐apoptotic functions of granzymes
Romero, V., & Andrade, F. (2008) · Tissue Antigens · doi:10.1111/j.1399-0039.2008.01013.x · Cited by 66 · see citing works
Fractalkine Promotes Human Monocyte Survival via a Reduction in Oxidative Stress
White, G. E., McNeill, E., Channon, K. M., & Greaves, D. R. (2014) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.114.304717 · Cited by 60 · see citing works
The transcriptome of human monocyte subsets begins to emerge
Martínez, F. O. (2009) · Journal of Biology · doi:10.1186/jbiol206 · Cited by 38 · see citing works
Infrastructure and resources for an aging population: embracing complexity in translational research
High, K. P. (2013) · Translational research · doi:10.1016/j.trsl.2013.09.001 · Cited by 12 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- [31]Huang da W Sherman BT Lempicki RA 2009 Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources Nature protocols 4 44 57 19131956
Cited by
Sorted by citations
The twilight of immunity: emerging concepts in aging of the immune system
Nikolich-Žugich, J. (2018) · Nature Immunology · doi:10.1038/s41590-017-0006-x · Cited by 1,240 · see citing works
Distinguishing features of long COVID identified through immune profiling
Klein, J., Wood, J., Jaycox, J. R., Dhodapkar, R. M., Lu, P., Gehlhausen, J. R., Tabachnikova, A., Greene, K., TABACOF, L. R., Malik, A. A., et al. (2023) · Nature · doi:10.1038/s41586-023-06651-y · Cited by 818 · see citing works
Immunosenescence and inflammaging in the aging process: age-related diseases or longevity?
Santoro, A., Bientinesi, E., & Monti, D. (2021) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101422 · Cited by 603 · see citing works
SARS-CoV-2, COVID-19 and the aging immune system
Bartleson, J. M., Radenkovic, D., Covarrubias, A. J., Furman, D., Winer, D. A., & Verdin, E. (2021) · Nature Aging · doi:10.1038/s43587-021-00114-7 · Cited by 359 · see citing works
The integration of inflammaging in age-related diseases
Fülöp, T., Witkowski, J. M., Olivieri, F., & Larbi, A. (2018) · Seminars in Immunology · doi:10.1016/j.smim.2018.09.003 · Cited by 356 · see citing works
The impact of ageing on monocytes and macrophages
De Maeyer, R. P. H., & Chambers, E. S. (2021) · Immunology Letters · doi:10.1016/j.imlet.2020.12.003 · Cited by 275 · see citing works
Oh, S. J., Lee, J. K., & Shin, O. S. (2019) · Immune Network · doi:10.4110/in.2019.19.e37 · Cited by 261 · see citing works
Mitochondrial function in immune cells in health and disease
Faas, M. M., & de Vos, P. (2020) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2020.165845 · Cited by 246 · see citing works
Frasca, D., Diaz, A., Romero, M., Garcia, D., & Blomberg, B. B. (2020) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-011620-034148 · Cited by 226 · see citing works
Ageing of the gut microbiome: Potential influences on immune senescence and inflammageing
Conway, J., & Duggal, N. A. (2021) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101323 · Cited by 194 · see citing works
I mmunosenescence and Inflammaging: Risk Factors of Severe COVID-19 in Older People
Pietrobon, A. J., Teixeira, F. M. E., & Sato, M. N. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.579220 · Cited by 185 · see citing works
TLR7 and TLR8 activate distinct pathways in monocytes during RNA virus infection
de Marcken, M., Dhaliwal, K., Danielsen, A. C., Gautron, A. S., & Dominguez‐Villar, M. (2019) · Science Signaling · doi:10.1126/scisignal.aaw1347 · Cited by 174 · see citing works
The origins and homeostasis of monocytes and tissue‐resident macrophages in physiological situation
Zhao, Y., Zou, W., Du, J., & Zhao, Y. (2018) · Journal of Cellular Physiology · doi:10.1002/jcp.26461 · Cited by 183 · see citing works
Dynamics of human monocytes and airway macrophages during healthy aging and after transplant
Byrne, A. J., Powell, J. E., O’Sullivan, B., Ogger, P. P., Hoffland, A., Cook, J., Bonner, K., Hewitt, R. J., Wolf, S., Ghai, P., et al. (2020) · The Journal of Experimental Medicine · doi:10.1084/jem.20191236 · Cited by 140 · see citing works
Immunology of the ageing kidney
Sato, Y., & Yanagita, M. (2019) · Nature Reviews Nephrology · doi:10.1038/s41581-019-0185-9 · Cited by 126 · see citing works
Human Monocyte Subset Distinctions and Function: Insights From Gene Expression Analysis
Cormican, S., & Griffin, M. D. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01070 · Cited by 126 · see citing works
Aging impairs mitochondrial respiratory capacity in classical monocytes
Pence, B. D., & Yarbro, J. R. (2018) · Experimental Gerontology · doi:10.1016/j.exger.2018.04.008 · Cited by 120 · see citing works
Macrophage metabolic reprogramming during chronic lung disease
Ogger, P. P., & Byrne, A. J. (2020) · Mucosal Immunology · doi:10.1038/s41385-020-00356-5 · Cited by 119 · see citing works
Single-cell landscape of peripheral immune responses to fatal SFTS
Li, H., Li, X., Lv, S., Peng, X., Cui, N., Yang, T., Yang, Z., Yuan, C., Yuan, Y., Yao, J., et al. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.110039 · Cited by 107 · see citing works
Immunosenescence in multiple sclerosis: the identification of new therapeutic targets
Dema, M. G., Eixarch, H., Villar, L. M., Montalbán, X., & Espejo, C. (2021) · Autoimmunity Reviews · doi:10.1016/j.autrev.2021.102893 · Cited by 101 · see citing works
Monocyte Differentiation and Heterogeneity: Inter-Subset and Interindividual Differences
Williams, H., Mack, C. D., Baraz, R., Marimuthu, R., Naralashetty, S., Li, S., & Medbury, H. J. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24108757 · Cited by 103 · see citing works
The 3 I’s of immunity and aging: immunosenescence, inflammaging, and immune resilience
Wrona, M. V., Ghosh, R. B., Coll, K., Chun, C., & Yousefzadeh, M. J. (2024) · Frontiers in Aging · doi:10.3389/fragi.2024.1490302 · Cited by 102 · see citing works
Monocytes present age-related changes in phospholipid concentration and decreased energy metabolism
Saare, M., Tserel, L., Haljasmägi, L., Taalberg, E., Peet, N., Eimre, M., Vetik, R., Kingo, K., Saks, K., Tamm, R., et al. (2020) · Aging Cell · doi:10.1111/acel.13127 · Cited by 79 · see citing works
Munawara, U., Catanzaro, M., Xu, W., Tan, C., Hirokawa, K., Bosco, N., Dumoulin, D., Khalil, A., Larbi, A., Lévesque, S., et al. (2021) · Immunity & Ageing · doi:10.1186/s12979-021-00236-x · Cited by 74 · see citing works
Trophoblast-secreted soluble-PD-L1 modulates macrophage polarization and function
Zhang, Y., Aldo, P. B., You, Y., Ding, J., Kaislasuo, J., Petersen, J. F., Løkkegaard, E., Peng, G., Paidas, M. J., Simpson, S., et al. (2020) · Journal of Leukocyte Biology · doi:10.1002/jlb.1a0420-012rr · Cited by 67 · see citing works
Aging, cancer, and antitumor immunity
Ikeda, H., & Togashi, Y. (2021) · International Journal of Clinical Oncology · doi:10.1007/s10147-021-01913-z · Cited by 65 · see citing works
Immunosenescence and inflamm-ageing in COVID-19
Zinatizadeh, M. R., Zarandi, P. K., Ghiasi, M., Kooshki, H., Mohammadi, M., Amani, J., & Rezaei, N. (2022) · Ageing Research Reviews · doi:10.1016/j.arr.2022.101818 · Cited by 62 · see citing works
Relationships Between Ion Channels, Mitochondrial Functions and Inflammation in Human Aging
Strickland, M., Yacoubi‐Loueslati, B., Bouhaouala‐Zahar, B., Pender, S. L. F., & Larbi, A. (2019) · Frontiers in Physiology · doi:10.3389/fphys.2019.00158 · Cited by 63 · see citing works
CCR2 is a host entry receptor for severe fever with thrombocytopenia syndrome virus
Zhang, L., Peng, X., Wang, Q., Jin, L., Lv, S., Han, S., Zhang, L., Ding, H., Wang, C., Xiao, G., et al. (2023) · Science Advances · doi:10.1126/sciadv.adg6856 · Cited by 60 · see citing works
Perdaens, O., & Pesch, V. V. (2022) · Frontiers in Neurology · doi:10.3389/fneur.2021.811518 · Cited by 59 · see citing works
Production of MHCII ‐expressing classical monocytes increases during aging in mice and humans
Barman, P. K., Shin, J. E., Lewis, S. A., Kang, S., Wu, D., Wang, Y., Yang, X., Nagarkatti, P. S., Nagarkatti, M., Messaoudi, I., et al. (2022) · Aging Cell · doi:10.1111/acel.13701 · Cited by 61 · see citing works
Aging and chronic kidney disease: epidemiology, therapy, management and the role of immunity
Tang, Y., Jiang, J., Zhao, Y., & Du, D. (2024) · Clinical Kidney Journal · doi:10.1093/ckj/sfae235 · Cited by 65 · see citing works
Innate Antiviral Immunity in the Skin
Handfield, C., Kwock, J. T., & MacLeod, A. S. (2018) · Trends in Immunology · doi:10.1016/j.it.2018.02.003 · Cited by 53 · see citing works
Aging and Options to Halt Declining Immunity to Virus Infections
Palacios-Pedrero, M. Á., Osterhaus, A. D. M. E., Becker, T., Elbahesh, H., Rimmelzwaan, G. F., & Saletti, G. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.681449 · Cited by 55 · see citing works
Immunotherapy in older patients with cancer
Granier, C., Gey, A., Roncelin, S., Weiss, L., Paillaud, É., & Tartour, É. (2020) · Biomedical Journal · doi:10.1016/j.bj.2020.07.009 · Cited by 56 · see citing works
Immunesenescence: A Predisposing Risk Factor for the Development of COVID-19?
Hazeldine, J., & Lord, J. M. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.573662 · Cited by 53 · see citing works
Reversing the immune ageing clock: lifestyle modifications and pharmacological interventions
Duggal, N. A. (2018) · Biogerontology · doi:10.1007/s10522-018-9771-7 · Cited by 53 · see citing works
The emerging role of T follicular helper (TFH) cells in aging: Influence on the immune frailty
Varricchi, G., Bencivenga, L., Poto, R., Pecoraro, A., Shamji, M. H., & Rengo, G. (2020) · Ageing Research Reviews · doi:10.1016/j.arr.2020.101071 · Cited by 52 · see citing works
Casaletto, K. B., Staffaroni, A. M., Elahi, F., Fox, E., Crittenden, P. A., You, M., Neuhaus, J., Glymour, M., Bettcher, B. M., Yaffe, K., et al. (2018) · The American Journal of Geriatric Psychiatry · doi:10.1016/j.jagp.2018.05.004 · Cited by 47 · see citing works
How Inflammation Blunts Innate Immunity in Aging
Goldberg, E. L., Shaw, A. C., & Montgomery, R. R. (2020) · Interdisciplinary topics in gerontology and geriatrics · doi:10.1159/000504480 · Cited by 45 · see citing works
Immunosenescence and multiple sclerosis: inflammaging for prognosis and therapeutic consideration
Thakolwiboon, S., Mills, E. A., Yang, J., Doty, J., Belkin, M., Cho, T., Schultz, C., & Mao‐Draayer, Y. (2023) · Frontiers in Aging · doi:10.3389/fragi.2023.1234572 · Cited by 45 · see citing works
Naicker, S. D., Cormican, S., Griffin, T. P., Maretto, S., Martin, W. P., Ferguson, J. P., Cotter, D., Connaughton, E. P., Dennedy, M. C., & Griffin, M. D. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02845 · Cited by 44 · see citing works
Age‐related factors that affect B cell responses to vaccination in mice and humans
Frasca, D., Blomberg, B. B., Garcia, D., Keilich, S. R., & Haynes, L. (2020) · Immunological Reviews · doi:10.1111/imr.12864 · Cited by 41 · see citing works
Monocytes in HIV and SIV Infection and Aging: Implications for Inflamm-Aging and Accelerated Aging
Wallis, Z. K., & Williams, K. C. (2022) · Viruses · doi:10.3390/v14020409 · Cited by 40 · see citing works
The diseased kidney: aging and senescent immunology
Chi, M., Tian, Z., Ma, K., Li, Y., Wang, L., Nasser, M. I., & Liu, C. (2022) · Immunity & Ageing · doi:10.1186/s12979-022-00313-9 · Cited by 41 · see citing works
The impact of immuno-aging on SARS-CoV-2 vaccine development
Connors, J. R., Bell, M. R., Marcy, J., Kutzler, M. A., & Haddad, E. K. (2021) · GeroScience · doi:10.1007/s11357-021-00323-3 · Cited by 38 · see citing works
Self-citationCellular Senescence in Immunity against Infections
Marrella, V., Facoetti, A., & Cassani, B. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms231911845 · Cited by 37 · see citing works
Tavenier, J., Rasmussen, L. J. H., Houlind, M. B., Andersen, A. L., Panum, I., Andersen, O., Petersen, J., Langkilde, A., & Nehlin, J. O. (2020) · Immunity & Ageing · doi:10.1186/s12979-020-00197-7 · Cited by 35 · see citing works
Compromised steady‐state germinal center activity with age in nonhuman primates
Shankwitz, K., Pallikkuth, S., Sirupangi, T., Kvistad, D., Russel, K. B., Pahwa, R., Gama, L., Koup, R. A., Pan, L., Villinger, F. J., et al. (2019) · Aging Cell · doi:10.1111/acel.13087 · Cited by 34 · see citing works
Adenosine deaminase-1 delineates human follicular helper T cell function and is altered with HIV
Tardif, V., Muir, R., Cubas, R. A., Chakhtoura, M., Wilkinson, P. A., Metcalf, T. U., Herro, R., & Haddad, E. K. (2019) · Nature Communications · doi:10.1038/s41467-019-08801-1 · Cited by 34 · see citing works
Self-citationAn old problem with new solutions: Strategies to improve vaccine efficacy in the elderly
Bell, M. R., & Kutzler, M. A. (2022) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2022.114175 · Cited by 29 · see citing works
Systemic immune response in young and elderly patients after traumatic brain injury
Magatti, M., Pischiutta, F., Ortolano, F., Pasotti, A., Caruso, E., Cargnoni, A., Papait, A., Capuzzi, F., Zoerle, T., Carbonara, M., et al. (2023) · Immunity & Ageing · doi:10.1186/s12979-023-00369-1 · Cited by 29 · see citing works
Avivi, I. M., Zisman‐Rozen, S., Naor, S., Dai, I., Benhamou, D., Shahaf, G. L., Tabibian‐Keissar, H., Rosenthal, N., Rakovsky, A., Ammuri, H., et al. (2019) · Aging Cell · doi:10.1111/acel.12959 · Cited by 30 · see citing works
Trained Immunity Enhances Human Monocyte Function in Aging and Sepsis
Gill, P. S., Ozment, T. R., Lewis, N. H., Sherwood, E. R., & Williams, D. L. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.872652 · Cited by 29 · see citing works
Targeting Impaired Antimicrobial Immunity in the Brain for the Treatment of Alzheimer’s Disease
Fülöp, T., Tripathi, S., Rodrigues, S., Desroches, M., Bunt, T., Eiser, A. R., Bernier, F., Beauregard, P. B., Barron, A. E., Khalil, A., et al. (2021) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s264910 · Cited by 27 · see citing works
Circulating biomarkers of inflammaging as potential predictors of COVID-19 severe outcomes
Sabbatinelli, J., Matacchione, G., Giuliani, A., Ramini, D., Rippo, M. R., Procopio, A. D., Bonafè, M., & Olivieri, F. (2022) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2022.111667 · Cited by 27 · see citing works
Phan, H. V., Tsitsiklis, A., Maguire, C. P., Haddad, E. K., Becker, P. M., Kim‐Schulze, S., Lee, B. H., Chen, J., Hoch, A., Pickering, H. C., et al. (2024) · Science Translational Medicine · doi:10.1126/scitranslmed.adj5154 · Cited by 27 · see citing works
Self-citationLongevity-Associated Variant of BPIFB4 Mitigates Monocyte-Mediated Acquired Immune Response
Ciaglia, E., Montella, F., Maciag, A. E., Scala, P., Ferrario, A., Banco, C., Carrizzo, A., Spinelli, C., Cattaneo, M., de Candia, P., et al. (2019) · The Journals of Gerontology Series A · doi:10.1093/gerona/glz036 · Cited by 26 · see citing works
Bissa, M., Kim, S., Galli, V., Fourati, S., Sarkis, S., Arakelyan, A., de Castro, I. S., Rahman, M. A., Fujiwara, S., Vaccari, M., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-36109-8 · Cited by 25 · see citing works
Self-citationLinked optical and gene expression profiling of single cells at high-throughput
Zhang, J. Q., Siltanen, C. A., Liu, L., Chang, K., Gartner, Z. J., & Abate, A. R. (2020) · Genome biology · doi:10.1186/s13059-020-01958-9 · Cited by 23 · see citing works
Prummel, K. D., Woods, K., Kholmatov, M. M., Schmitt, E. C., Vlachou, E. P., Labyadh, M., Wehner, R., Poschmann, G., Stühler, K., Winter, S., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-65803-y · Cited by 26 · see citing works
Sandionigi, A., Giani, A. D., Tursi, F., Michelotti, A., Cestone, E., Giardina, S., Zampolli, J., & Gennaro, P. D. (2022) · BioMed Research International · doi:10.1155/2022/3860896 · Cited by 24 · see citing works
Connors, J. R., Taramangalam, B., Cusimano, G. M., Bell, M. R., Matt, S. M., Runner, K., Gaskill, P. J., DeFilippis, V. R., Nikolich‐Žugich, J., Kutzler, M. A., et al. (2022) · GeroScience · doi:10.1007/s11357-022-00612-5 · Cited by 24 · see citing works
Self-citationZhou, M., Zhang, H., Bai, Z., Mann‐Krzisnik, D., Wang, F., & Li, Y. (2023) · Cell Reports Methods · doi:10.1016/j.crmeth.2023.100563 · Cited by 22 · see citing works
George, V. K., Pallikkuth, S., Pahwa, R., de Armas, L. R., Rinaldi, S., Pan, L., & Pahwa, S. G. (2018) · AIDS · doi:10.1097/qad.0000000000001821 · Cited by 24 · see citing works
Emergence of T cell immunosenescence in diabetic chronic kidney disease
Chiu, Y., Tsai, W., Hung, R., Chen, I., Shu, K.-H., Pan, S., Yang, F., Ting, T., Jiang, J., Peng, Y., et al. (2020) · Immunity & Ageing · doi:10.1186/s12979-020-00200-1 · Cited by 25 · see citing works
New Pharmacological Tools to Target Leukocyte Trafficking in Lung Disease
Belchamber, K. B. R., Hughes, M., Spittle, D. A., Walker, E. M., & Sapey, E. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.704173 · Cited by 21 · see citing works
Farheen, S., Agrawal, S., Zubair, S., Agrawal, A., Jamal, F., Altaf, I., Anwar, A. K., Umair, S. M., & Owais, M. (2021) · Frontiers in Aging · doi:10.3389/fragi.2021.748591 · Cited by 23 · see citing works
Aldriwesh, M. G., Alotibi, R. S., Alqurainy, N., Alrabiah, S., Arafah, A. M., Alghoribi, M. F., & Ajina, R. (2025) · Gut Microbes · doi:10.1080/19490976.2025.2607076 · Cited by 20 · see citing works
Liu, Z., Jiang, Z., Zhang, L., Xue, X., Zhao, C., Xu, Y., Zhang, W., Lin, L., & Chen, Z. (2024) · Frontiers in Microbiology · doi:10.3389/fmicb.2023.1307960 · Cited by 20 · see citing works
Gorini, G., Fourati, S., Vaccari, M., Rahman, M. A., Gordon, S. N., Brown, D. R., Law, G. L., Chang, J., Green, R. R., Barrenäs, F., et al. (2020) · PLoS Pathogens · doi:10.1371/journal.ppat.1008377 · Cited by 20 · see citing works
Li, M., Xie, Z., Cai, Z., Su, F., Guan, Z., Li, J., Wang, S., Cen, S., Liu, W., Tang, S., et al. (2019) · Stem Cell Research & Therapy · doi:10.1186/s13287-019-1306-x · Cited by 19 · see citing works
Platelet-derived β2m regulates age related monocyte/macrophage functions
Hilt, Z. T., Ture, S. K., Mohan, A. M., Arne, A., & Morrell, C. N. (2019) · Aging · doi:10.18632/aging.102520 · Cited by 18 · see citing works
Immune Cells and Immunosenescence
Bischof, J., Gärtner, F., Zeiser, K., Kunz, R., Schreiner, C., Hoffer, E., Burster, T., Knippschild, U., & Zimecki, M. (2019) · Folia Biologica · doi:10.14712/fb2019065020053 · Cited by 18 · see citing works
Liang, X., Sinha, R., Justice, A. C., Cohen, M. H., Aouizerat, B. E., & Xu, K. (2022) · Alcoholism Clinical and Experimental Research · doi:10.1111/acer.14803 · Cited by 17 · see citing works
Immunity to acute virus infections with advanced age
Nikolich‐Žugich, J., Bradshaw, C. M., Uhrlaub, J. L., & Watanabe, M. (2020) · Current Opinion in Virology · doi:10.1016/j.coviro.2020.09.007 · Cited by 17 · see citing works
Suehiro, H., Kiuchi, K., Fukuzawa, K., Yoshida, N., Takami, M., Watanabe, Y., Izawa, Y., Akita, T., Takemoto, M., Sakai, J., et al. (2021) · Journal of Cardiovascular Electrophysiology · doi:10.1111/jce.14929 · Cited by 17 · see citing works
Macrophage re-programming by JAK inhibitors relies on MAFB
López-Navarro, B., Simón‐Fuentes, M., Ríos, I., Schiaffino, M. T., Sánchez, A., Torres‐Torresano, M., Nieto‐Valle, A., Castrejón, I., & Puig‐Kröger, A. (2024) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-024-05196-1 · Cited by 19 · see citing works
Ascoli, C., Schott, C. A., Huang, Y., Turturice, B. A., Wang, W., Ecanow, N. S., Sweiss, N., Perkins, D. L., & Finn, P. W. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.848759 · Cited by 17 · see citing works
Yin, F., He, Y., Li, J., & Gao, Y. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1596686 · Cited by 16 · see citing works
Pirabe, A., Heber, S., Schrottmaier, W. C., Schmuckenschlager, A., Treiber, S. M., Pereyra, D., Santol, J., Pawelka, E., Traugott, M. T., Schoergenhofer, C., et al. (2021) · Cells · doi:10.3390/cells10123373 · Cited by 16 · see citing works
Aging and Microbiome in the Modulation of Vaccine Efficacy
Kumar, M., James, M. M., Kumawat, M., Nabi, B., Sharma, P., Pal, N., Shubham, S., Tiwari, R. R., Sarma, D. K., & Nagpal, R. (2022) · Biomedicines · doi:10.3390/biomedicines10071545 · Cited by 15 · see citing works
Transcriptional characteristics and functional validation of three monocyte subsets during aging
Wang, C., Cheng, Y., Li, B., Qiu, X., Hu, H., Zhang, X., Lu, Z., & Zheng, F. (2023) · Immunity & Ageing · doi:10.1186/s12979-023-00377-1 · Cited by 15 · see citing works
Immune profiling of age and adjuvant-specific activation of human blood mononuclear cells in vitro
Schüller, S. S., Barman, S., Méndez-Giráldez, R., Soni, D., Daley, J. F., Baden, L. R., Levy, O., & Dowling, D. J. (2024) · Communications Biology · doi:10.1038/s42003-024-06390-4 · Cited by 15 · see citing works
Maeyer, R. P. H. D., Sikora, J., Bracken, O. V., Shih, B. B.-J., Lloyd, A. F., Peckham, H., Hollett, K., Abdelhamid, K., Cai, W., James, M., et al. (2025) · Aging Cell · doi:10.1111/acel.70249 · Cited by 15 · see citing works
Hoffmann, J., Fišer, K., Liebetrau, C., Staubach, N., Kost, D., Voss, S., Heiden, A. Z., Dörr, O., Lipps, C., NEF, H. M., et al. (2019) · Thrombosis and Haemostasis · doi:10.1055/s-0039-1700871 · Cited by 14 · see citing works
Dobbs, K. R., Embury, P., Koech, E., Ogolla, S., Munga, S., Kazura, J. W., & Dent, A. E. (2021) · Immunity & Ageing · doi:10.1186/s12979-021-00223-2 · Cited by 13 · see citing works
Cooper, D. M., & Radom‐Aizik, S. (2019) · Pediatric Research · doi:10.1038/s41390-019-0581-7 · Cited by 17 · see citing works
Guan, X., Zha, L., Zhu, X., Rao, X., Huang, X., Xiong, Y., Guo, Y., Zhang, M., Zhou, D., Tu, Q., et al. (2025) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2025.5588 · Cited by 13 · see citing works
Nucleic acid vaccines: innovations, efficacy, and applications in at-risk populations
Konopka, E., Edgerton, A. O., & Kutzler, M. A. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1584876 · Cited by 13 · see citing works
Adjuvant AS01 activates human monocytes for costimulation and systemic inflammation
Smith, C. L., Richardson, B., Rubsamen, M., Cameron, M. J., Cameron, C., & Canaday, D. H. (2023) · Vaccine · doi:10.1016/j.vaccine.2023.12.010 · Cited by 13 · see citing works
Self-citationUsing the power of innate immunoprofiling to understand vaccine design, infection, and immunity
Connors, J. R., Cusimano, G. M., Mege, N. J., Woloszczuk, K., Konopka, E., Bell, M. R., Joyner, D., Marcy, J., Tardif, V., Kutzler, M. A., et al. (2023) · Human Vaccines & Immunotherapeutics · doi:10.1080/21645515.2023.2267295 · Cited by 12 · see citing works
Self-citationTriggering Innate Immune Receptors as New Therapies in Alzheimer’s Disease and Multiple Sclerosis
Piec, P.-A., Pons, V., & Rivest, S. (2021) · Cells · doi:10.3390/cells10082164 · Cited by 10 · see citing works
The slan antigen identifies the prototypical non-classical CD16+-monocytes in human blood
Tamassia, N., Bianchetto-Aguilera, F. M., Gasperini, S., Grimaldi, A., Montaldo, C., Calzetti, F., Gardiman, E., Signoretto, I., Castellucci, M., Barnaba, V., et al. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1287656 · Cited by 9 · see citing works
Tampé, J., Monni, E., Palma-Tortosa, S., Brogårdh, E., Böiers, C., Lindgren, A. G., & Kokaia, Z. (2024) · PLoS ONE · doi:10.1371/journal.pone.0300946 · Cited by 9 · see citing works
Lázničková, P., Bendíčková, K., Kepák, T., & Frič, J. (2021) · Frontiers in Aging · doi:10.3389/fragi.2021.708788 · Cited by 9 · see citing works
Kumar, A., Wang, J., Esterly, A. T., Radcliffe, C., Zhou, H., Wyk, B. V., Allore, H. G., Tsang, S. W., Barakat, L., Mohanty, S., et al. (2023) · Aging · doi:10.18632/aging.204927 · Cited by 8 · see citing works
A missense variant in the nuclear localization signal of DKC1 causes Hoyeraal-Hreidarsson syndrome
Chu, C.-M., Yu, H., Kao, T.-L., Chen, Y.-H., Lu, H., Wu, E., Yang, Y., Lin, C., Lin, S., Tsai, M.-J. M., et al. (2022) · npj Genomic Medicine · doi:10.1038/s41525-022-00335-8 · Cited by 8 · see citing works
Regulatory RNAs in immunosenescence
Talepoor, A. G., & Doroudchi, M. (2024) · Immunity Inflammation and Disease · doi:10.1002/iid3.1209 · Cited by 7 · see citing works
Wen, Y., Tong, Y., Gong, L., Li, A., Huang, X., Tian, T., Liu, T., Sun, L., Li, J., Li, D., et al. (2025) · Biosafety and Health · doi:10.1016/j.bsheal.2025.03.005 · Cited by 7 · see citing works
- Authors
- Metcalf, T. U., Wilkinson, P. A., Cameron, M. J., Ghneim, K., Chiang, C., Wertheimer, A. M., Hiscott, J. B., Nikolich-Zugich, J., & Haddad, E. K.
- Affiliations
- Drexel University (US)
- Case Western Reserve University (US)
- University of Chicago (US)
- University of Arizona (US)
- Istituto Pasteur (IT)
- Department of Immunobiology, University of Arizona College of Medicine , Tucson, AZ 85724
- Corresponding author
- Haddad, Elias K
- ORCID
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2017-08
- Volume
- 199
- Issue
- 4
- Pages
- 1405-1417
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- PMC
- PMC5548610
- OpenAlex
- W2735891807
- Cited by
- 166
- References
- 49
- Citations by year
- 2026: 10 · 2025: 13 · 2024: 20 · 2023: 25 · 2022: 20 · 2021: 27 · 2020: 23 · 2019: 16 · 2018: 10 · 2017: 2
- FWCI
- 6.31
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Case Western Reserve University
- National Institute of Allergy and Infectious Diseases (HHSN272201400055C, HHSN272201100017C)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Keywords
- aging, monocytes, monocyte subsets, pattern recognition receptors, TLR4, TLR7/8, RIG-I, interferon production, CX3CR1, CCL20, CCL8, IL-1β, immunosenescence, vaccine response, infection susceptibility
- MeSH terms
- Adult, Aged, Aged, 80 and over, Aging, Female, Humans, Immunity, Innate, Interferons, Male, Middle Aged, Monocytes, Transcription, Genetic, Cytokines, Receptors, IgG, Lipopolysaccharide Receptors, Gene Expression Profiling, Receptors, Pattern Recognition, Toll-Like Receptor 4, Toll-Like Receptor 7, Toll-Like Receptor 8, Young Adult, GPI-Linked Proteins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
