Markers of systemic inflammation are positively associated with influenza vaccine antibody responses with a possible role for ILT2(+)CD57(+) NK-cells
Abstract Background With increasing age, overall health declines while systemic levels of inflammatory mediators tend to increase. Although the underlying mechanisms are poorly understood, there is a wealth of data suggesting that this so-called “inflammaging” contributes to the risk of adverse outc...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-05-01
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| Series: | Immunity & Ageing |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12979-022-00284-x |
| _version_ | 1828223219427966976 |
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| author | Emilie Picard Sarah Armstrong Melissa K. Andrew Laura Haynes Mark Loeb Graham Pawelec George A. Kuchel Janet E. McElhaney Chris P. Verschoor |
| author_facet | Emilie Picard Sarah Armstrong Melissa K. Andrew Laura Haynes Mark Loeb Graham Pawelec George A. Kuchel Janet E. McElhaney Chris P. Verschoor |
| author_sort | Emilie Picard |
| collection | DOAJ |
| description | Abstract Background With increasing age, overall health declines while systemic levels of inflammatory mediators tend to increase. Although the underlying mechanisms are poorly understood, there is a wealth of data suggesting that this so-called “inflammaging” contributes to the risk of adverse outcomes in older adults. We sought to determine whether markers of systemic inflammation were associated with antibody responses to the seasonal influenza vaccine. Results Over four seasons, hemagglutination inhibition antibody titres and ex vivo bulk peripheral blood mononuclear cell (PBMC) responses to live influenza viruses assessed via interferon (IFN)-γ/interleukin (IL)-10 production, were measured pre- and 4-weeks post-vaccination in young adults (n = 79) and older adults randomized to standard- or high-dose inactivated vaccine (n = 612). Circulating tumour necrosis factor (TNF), interleukin (IL)-6 and C-reactive protein (CRP) were also measured pre-vaccination. Post-vaccination antibody titres were significantly associated with systemic inflammatory levels; specifically, IL-6 was positively associated with A/H3N2 titres in young adults (Cohen’s d = 0.36), and in older high-dose, but not standard-dose recipients, all systemic inflammatory mediators were positively associated with A/H1N1, A/H3N2 and B titres (d = 0.10–0.45). We further show that the frequency of ILT2(+)CD57(+) CD56-Dim natural killer (NK)-cells was positively associated with both plasma IL-6 and post-vaccination A/H3N2 titres in a follow-up cohort of older high-dose recipients (n = 63). Pathway analysis suggested that ILT2(+)CD57(+) Dim NK-cells mediated 40% of the association between IL-6 and A/H3N2 titres, which may be related to underlying participant frailty. Conclusions In summary, our data suggest a complex relationship amongst influenza vaccine responses, systemic inflammation and NK-cell phenotype in older adults, which depends heavily on age, vaccine dose and possibly overall health status. While our results suggest that “inflammaging” may increase vaccine immunogenicity in older adults, it is yet to be determined whether this enhancement contributes to improved protection against influenza disease. |
| first_indexed | 2024-04-12T17:04:23Z |
| format | Article |
| id | doaj.art-7ebbef19822844c38fada3f9ca189613 |
| institution | Directory Open Access Journal |
| issn | 1742-4933 |
| language | English |
| last_indexed | 2024-04-12T17:04:23Z |
| publishDate | 2022-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Immunity & Ageing |
| spelling | doaj.art-7ebbef19822844c38fada3f9ca1896132022-12-22T03:23:59ZengBMCImmunity & Ageing1742-49332022-05-0119111410.1186/s12979-022-00284-xMarkers of systemic inflammation are positively associated with influenza vaccine antibody responses with a possible role for ILT2(+)CD57(+) NK-cellsEmilie Picard0Sarah Armstrong1Melissa K. Andrew2Laura Haynes3Mark Loeb4Graham Pawelec5George A. Kuchel6Janet E. McElhaney7Chris P. Verschoor8Health Sciences North Research InstituteHealth Sciences North Research InstituteDepartment of Medicine, Dalhousie UniversityUConn Center On Aging, University of Connecticut School of MedicineDepartment of Pathology and Molecular Medicine, McMaster UniversityHealth Sciences North Research InstituteUConn Center On Aging, University of Connecticut School of MedicineHealth Sciences North Research InstituteHealth Sciences North Research InstituteAbstract Background With increasing age, overall health declines while systemic levels of inflammatory mediators tend to increase. Although the underlying mechanisms are poorly understood, there is a wealth of data suggesting that this so-called “inflammaging” contributes to the risk of adverse outcomes in older adults. We sought to determine whether markers of systemic inflammation were associated with antibody responses to the seasonal influenza vaccine. Results Over four seasons, hemagglutination inhibition antibody titres and ex vivo bulk peripheral blood mononuclear cell (PBMC) responses to live influenza viruses assessed via interferon (IFN)-γ/interleukin (IL)-10 production, were measured pre- and 4-weeks post-vaccination in young adults (n = 79) and older adults randomized to standard- or high-dose inactivated vaccine (n = 612). Circulating tumour necrosis factor (TNF), interleukin (IL)-6 and C-reactive protein (CRP) were also measured pre-vaccination. Post-vaccination antibody titres were significantly associated with systemic inflammatory levels; specifically, IL-6 was positively associated with A/H3N2 titres in young adults (Cohen’s d = 0.36), and in older high-dose, but not standard-dose recipients, all systemic inflammatory mediators were positively associated with A/H1N1, A/H3N2 and B titres (d = 0.10–0.45). We further show that the frequency of ILT2(+)CD57(+) CD56-Dim natural killer (NK)-cells was positively associated with both plasma IL-6 and post-vaccination A/H3N2 titres in a follow-up cohort of older high-dose recipients (n = 63). Pathway analysis suggested that ILT2(+)CD57(+) Dim NK-cells mediated 40% of the association between IL-6 and A/H3N2 titres, which may be related to underlying participant frailty. Conclusions In summary, our data suggest a complex relationship amongst influenza vaccine responses, systemic inflammation and NK-cell phenotype in older adults, which depends heavily on age, vaccine dose and possibly overall health status. While our results suggest that “inflammaging” may increase vaccine immunogenicity in older adults, it is yet to be determined whether this enhancement contributes to improved protection against influenza disease.https://doi.org/10.1186/s12979-022-00284-xInfluenza vaccine responseInflammationILT2 + CD57 + NK cellsIL-6Older adultsFrailty |
| spellingShingle | Emilie Picard Sarah Armstrong Melissa K. Andrew Laura Haynes Mark Loeb Graham Pawelec George A. Kuchel Janet E. McElhaney Chris P. Verschoor Markers of systemic inflammation are positively associated with influenza vaccine antibody responses with a possible role for ILT2(+)CD57(+) NK-cells Immunity & Ageing Influenza vaccine response Inflammation ILT2 + CD57 + NK cells IL-6 Older adults Frailty |
| title | Markers of systemic inflammation are positively associated with influenza vaccine antibody responses with a possible role for ILT2(+)CD57(+) NK-cells |
| title_full | Markers of systemic inflammation are positively associated with influenza vaccine antibody responses with a possible role for ILT2(+)CD57(+) NK-cells |
| title_fullStr | Markers of systemic inflammation are positively associated with influenza vaccine antibody responses with a possible role for ILT2(+)CD57(+) NK-cells |
| title_full_unstemmed | Markers of systemic inflammation are positively associated with influenza vaccine antibody responses with a possible role for ILT2(+)CD57(+) NK-cells |
| title_short | Markers of systemic inflammation are positively associated with influenza vaccine antibody responses with a possible role for ILT2(+)CD57(+) NK-cells |
| title_sort | markers of systemic inflammation are positively associated with influenza vaccine antibody responses with a possible role for ilt2 cd57 nk cells |
| topic | Influenza vaccine response Inflammation ILT2 + CD57 + NK cells IL-6 Older adults Frailty |
| url | https://doi.org/10.1186/s12979-022-00284-x |
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