# Respiratory virus immune response in the aged host **Authors:** Olivia B. Parks, Anusha Kalavacharla, John V. Williams PMC · DOI: 10.1186/s12979-026-00559-7 · Immunity & Ageing : I & A · 2026-02-10 ## TL;DR This paper reviews how the aging immune system responds to respiratory viruses and highlights challenges in vaccine efficacy for older adults. ## Contribution The paper consolidates current knowledge and identifies gaps in understanding the aged immune response to respiratory viruses. ## Key findings - Aging impairs innate and adaptive immune cells, reducing the response to respiratory viruses. - The 'inflammaging' hypothesis links chronic inflammation to weakened immune responses in older adults. - Current vaccines for respiratory viruses are less effective in the elderly due to immune system decline. ## Abstract Viruses are a major cause of acute respiratory illness in older adults and pose a substantial burden as the elderly population continues to grow. In the current COVID-19 global health crisis, achieving a better understanding of the aging immune system proves to be an imperative step in preventing and treating respiratory viral infections in older patients. Furthermore, many common respiratory viruses infecting older adults, including human metapneumovirus and parainfluenza virus, do not have licensed vaccines, thereby increasing the risk of severe infection in the aged host. Moreover, given the slowed immune response of older adults, vaccine efficacy for respiratory viruses such as influenza in older adults is minimal, indicating the need to develop more potent vaccines. A better understanding of the aging immune system would allow vaccines to target immunological deficits in the aged host. Three aspects of the aging immune system affect the response to respiratory viruses and vaccines: [1] innate immunity [2], the “inflammaging” hypothesis, and [3] the adaptive immune response. Several innate immune cells (neutrophils, macrophages, dendritic cells, and natural killer cells) as well as adaptive immune cells (T and B lymphocytes) exhibit significant functional impairment in older adults. The inflammaging hypothesis bridges the innate and adaptive arms of the immune system. This review aims to consolidate current knowledge and fill gaps in our understanding of the aged immune response to respiratory viruses. ## Linked entities - **Diseases:** breast cancer (MONDO:0004989) ## Full-text entities - **Genes:** Cd44 (CD44 antigen) [NCBI Gene 12505] {aka HERMES, Ly-24, Pgp-1}, Trav6-3 (T cell receptor alpha variable 6-3) [NCBI Gene 328483] {aka Gm13948, Gm193, Gm4, TCR}, Ccl5 (C-C motif chemokine ligand 5) [NCBI Gene 20304] {aka MuRantes, RANTES, SISd, Scya5, TCP228}, Ighd (immunoglobulin heavy constant delta) [NCBI Gene 380797] {aka IgD, Igh-5}, Il1b (interleukin 1 beta) [NCBI Gene 16176] {aka IL-1beta, Il-1b}, Cd27 (CD27 antigen) [NCBI Gene 21940] {aka S152, Tnfrsf7, Tp55}, Il17a (interleukin 17A) [NCBI Gene 16171] {aka Ctla-8, Ctla8, IL-17, IL-17A, Il17}, Cxcr6 (C-X-C motif chemokine receptor 6) [NCBI Gene 80901] {aka BONZO, STRL33}, Cd86 (CD86 antigen) [NCBI Gene 12524] {aka B7, B7-2, B7.2, B70, CLS1, Cd28l2}, Tgfb1 (transforming growth factor, beta 1) [NCBI Gene 21803] {aka TGF-beta1, TGFbeta1, Tgfb, Tgfb-1}, Nt5e (5' nucleotidase, ecto) [NCBI Gene 23959] {aka 2210401F01Rik, 5'-NT, CD73, NT, Nt5, eNT}, Il15 (interleukin 15) [NCBI Gene 16168] {aka IL-15}, Il23a (interleukin 23, alpha subunit p19) [NCBI Gene 83430] {aka IL-23, p19}, Tnf (tumor necrosis factor) [NCBI Gene 21926] {aka DIF, TNF-a, TNF-alpha, TNFSF2, TNFalpha, Tnfa}, Mpo (myeloperoxidase) [NCBI Gene 17523] {aka mKIAA4033}, TBX21 (T-box transcription factor 21) [NCBI Gene 30009] {aka IMD88, T-PET, T-bet, TBET, TBLYM}, Ccnd1 (cyclin D1) [NCBI Gene 12443] {aka CycD1, Cyl-1, PRAD1, bcl-1, cD1}, Il10 (interleukin 10) [NCBI Gene 16153] {aka CSIF, If2a, Il-10}, Tlr9 (toll-like receptor 9) [NCBI Gene 81897], Bcl2 (B cell leukemia/lymphoma 2) [NCBI Gene 12043] {aka Bcl-2, C430015F12Rik, D630044D05Rik, D830018M01Rik}, H2 (histocompatibility-2, MHC) [NCBI Gene 111364] {aka H-2, MHC-II}, Il1rn (interleukin 1 receptor antagonist) [NCBI Gene 16181] {aka F630041P17Rik, IL-1ra}, Mtor (mechanistic target of rapamycin kinase) [NCBI Gene 56717] {aka 2610315D21Rik, FRAP, FRAP2, Frap1, RAFT1, RAPT1}, Igh (immunoglobulin heavy chain complex) [NCBI Gene 111507], Crp (C-reactive protein, pentraxin-related) [NCBI Gene 12944], Il4 (interleukin 4) [NCBI Gene 16189] {aka BSF-1, Il-4}, Cxcl2 (C-X-C motif chemokine ligand 2) [NCBI Gene 20310] {aka CINC-2a, GROb, Gro2, MIP-2, MIP-2a, Mgsa-b}, Cd68 (CD68 antigen) [NCBI Gene 12514] {aka Lamp4, Scard1, gp110}, Cd19 (CD19 antigen) [NCBI Gene 12478], Bcr (BCR activator of RhoGEF and GTPase) [NCBI Gene 110279] {aka 5133400C09Rik, mKIAA3017}, Apc (APC, WNT signaling pathway regulator) [NCBI Gene 11789] {aka CC1, Min, mAPC}, Cxcl1 (C-X-C motif chemokine ligand 1) [NCBI Gene 14825] {aka Fsp, Gro1, KC, Mgsa, N51, Scyb1}, Cxcl16 (C-X-C motif chemokine ligand 16) [NCBI Gene 66102] {aka 0910001K24Rik, CXCL16v1, CXCL16v2, SR-PSOX, Zmynd15, b2b498Clo}, Serpinb1-ps1 (serine (or cysteine) peptidase inhibitor, clade B, member 1, pseudogene) [NCBI Gene 282665] {aka EID, ovalbumin}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, Csf2 (colony stimulating factor 2 (granulocyte-macrophage)) [NCBI Gene 12981] {aka CSF, Csfgm, GMCSF, Gm-CSf, MGI-IGM}, Tlr4 (toll-like receptor 4) [NCBI Gene 21898] {aka Lps, Ly87, Ran/M1, Rasl2-8}, Cd69 (CD69 antigen) [NCBI Gene 12515] {aka 5830438K24Rik, AIM, VEA}, Gzmb (granzyme B) [NCBI Gene 14939] {aka CCP-1/C11, CCP1, Ctla-1, Ctla1, GZB}, Lag3 (lymphocyte-activation gene 3) [NCBI Gene 16768] {aka CD223, LAG-3, Ly66}, Tnfrsf1a (tumor necrosis factor receptor superfamily, member 1a) [NCBI Gene 21937] {aka CD120a, FPF, TNF-R, TNF-R-I, TNF-R1, TNF-R55}, Cd14 (CD14 antigen) [NCBI Gene 12475], Klf4 (Kruppel-like transcription factor 4 (gut)) [NCBI Gene 16600] {aka EZF, Gklf, Zie}, Zap70 (zeta-chain (TCR) associated protein kinase) [NCBI Gene 22637] {aka Srk, ZAP-70, mrtle, mur}, Fcgr3 (Fc receptor, IgG, low affinity III) [NCBI Gene 14131] {aka CD16}, ITGAX (integrin subunit alpha X) [NCBI Gene 3687] {aka CD11C, SLEB6}, Gdf15 (growth differentiation factor 15) [NCBI Gene 23886] {aka MIC-1, NAG-1, SBF}, Il17f (interleukin 17F) [NCBI Gene 257630] {aka IL-17F}, Ifng (interferon gamma) [NCBI Gene 15978] {aka IFN-g, If2f, Ifg}, Tradd (TNFRSF1A-associated via death domain) [NCBI Gene 71609] {aka 9130005N23Rik}, ITGAM (integrin subunit alpha M) [NCBI Gene 3684] {aka CD11B, CR3A, HNA-4, MAC-1, MAC1A, MO1A}, Il2ra (interleukin 2 receptor, alpha chain) [NCBI Gene 16184] {aka CD25, Il2r, Ly-43}, Foxp3 (forkhead box P3) [NCBI Gene 20371] {aka JM2, scurfin, sf}, Entpd1 (ectonucleoside triphosphate diphosphohydrolase 1) [NCBI Gene 12495] {aka 2610206B08Rik, ATP-DPH, Cd39, E130009M23Rik, NTPDase-1}, Cish (cytokine inducible SH2-containing protein) [NCBI Gene 12700] {aka CIS-1, CIS1, Cis, F17, F23, SOCS}, Ptprc (protein tyrosine phosphatase receptor type C) [NCBI Gene 19264] {aka B220, CD45R, Cd45, L-CA, Ly-5, Lyt-4}, Tlr7 (toll-like receptor 7) [NCBI Gene 170743], Ifna (interferon alpha complex region) [NCBI Gene 111654] {aka Ifa, Ifa8}, Ptpn6 (protein tyrosine phosphatase, non-receptor type 6) [NCBI Gene 15170] {aka 70Z-SHP, Hcph, PTPTY-42, Ptp1C, SH-PTP1, SHP-1}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4} - **Diseases:** atherosclerosis (MESH:D050197), Chronic viral infection (MESH:D014777), neutropenia (MESH:D009503), respiratory disease (MESH:D012140), deaths (MESH:D003643), Influenza infection (MESH:D007251), pneumococcal bacterial (MESH:D011008), immune impairment (MESH:D020274), Chronic inflammation (MESH:D007249), bacterial co-infection (MESH:D060085), lung T cell impairment (MESH:C536780), respiratory infections (MESH:D012141), age (MESH:D019588), cancer (MESH:D009369), parainfluenza (MESH:D018184), peritonitis (MESH:D010538), immune dysfunction (MESH:D007154), lung damage (MESH:D008171), COVID (MESH:D000086382), diabetes (MESH:D003920), infection (MESH:D007239), RSV infection (MESH:D018357), Alzheimer's (MESH:D000544), pneumonia (MESH:D011014), bacterial pneumonia (MESH:D018410), CMV (MESH:D003586), autoimmune (MESH:D001327), bacterial infection (MESH:D001424), type 2 diabetes (MESH:D003924), enteritis (MESH:D004751), in innate and adaptive immunity (MESH:D018489), systemic disease (MESH:D034721), infectious disease (MESH:D003141), chronic disease (MESH:D002908), RSV bronchiolitis (MESH:D001988) - **Chemicals:** ASO3 (-), quercetin (MESH:D011794), cortisol (MESH:D006854), dasatinib (MESH:D000069439), cysteine (MESH:D003545), LPS (MESH:D008070), metformin (MESH:D008687), MF59 (MESH:C089950), beta-glucan (MESH:D047071) - **Species:** Viruses (acellular root) [taxon 10239], Respiratory syncytial virus (no rank) [taxon 12814], Homo sapiens (human, species) [taxon 9606], Enterovirus (genus) [taxon 12059], Mus musculus (house mouse, species) [taxon 10090], Bacteria Latreille et al. 1825 (Bacteria stick insect, genus) [taxon 629395], human gammaherpesvirus 4 (Epstein Barr virus, no rank) [taxon 10376], Severe acute respiratory syndrome coronavirus 2 (no rank) [taxon 2697049], Human alphaherpesvirus 2 (no rank) [taxon 10310], human metapneumovirus (no rank) [taxon 162145], Cytomegalovirus (genus) [taxon 10358] - **Cell lines:** C57BL/6 — Mus musculus (Mouse), Transformed cell line (CVCL_C0MU), /6 — Homo sapiens (Human), Tongue squamous cell carcinoma, Cancer cell line (CVCL_5985) ## Full text _Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12922206/full.md ## Figures 1 figure with captions in the complete paper: https://tomesphere.com/paper/PMC12922206/full.md ## References 8 references — full list in the complete paper: https://tomesphere.com/paper/PMC12922206/full.md --- Source: https://tomesphere.com/paper/PMC12922206