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. 2021 Aug 20:2:719103.
doi: 10.3389/fragi.2021.719103. eCollection 2021.

Inflammasome Activity in Response to Influenza Vaccination Is Maintained in Monocyte-Derived Peripheral Blood Macrophages in Older Adults

Stephen N Crooke  1 , Krista M Goergen  2 , Inna G Ovsyannikova  1 , Richard B Kennedy  1
Affiliations

Inflammasome Activity in Response to Influenza Vaccination Is Maintained in Monocyte-Derived Peripheral Blood Macrophages in Older Adults

Stephen N Crooke et al. Front Aging. .

Abstract

Introduction: Each year, a disproportionate number of the total seasonal influenza-related hospitalizations (90%) and deaths (70%) occur among adults who are >65 years old. Inflammasome activation has been shown to be important for protection against influenza infection in animal models but has not yet been demonstrated in humans. We hypothesized that age-related dysfunction (immunosenescence) of the inflammasome may be associated with poor influenza-vaccine response among older adults. Methods: A cohort of younger (18-40 years of age) and older (≥65 years of age) adults was recruited prior to the 2014-2015 influenza season. We measured hemagglutination inhibition (HAI) titers in serum before and 28 days after receipt of the seasonal inactivated influenza vaccine. Inflammasome-related gene expression and protein secretion were quantified in monocyte-derived macrophages following stimulation with influenza A/H1N1 virus. Results: Younger adults exhibited higher HAI titers compared to older adults following vaccination, although inflammasome-related protein secretion in response to influenza stimulation was similar between the age groups. Expression of P2RX7 following influenza stimulation was lower among older adults. Interestingly, CFLAR expression was significantly higher among females (p = 2.42 × 10-5) following influenza stimulation and this gene may play an important role in the development of higher HAI antibody titers among older females. Conclusion: Inflammasome activation in response to influenza vaccination appears to be maintained in monocyte-derived macrophages from older adults and does not explain the poor influenza vaccine responses generally observed among this age group.

Keywords: NLRP3; aging; inflammasome; influenza; vaccination.

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Conflict of interest statement

IO hold three patents related to measles and vaccinia peptide research. RK holds a patent on vaccinia peptide research. RK and IO have received grant funding from ICW Ventures for preclinical studies on a peptide-based COVID-19 vaccine. RK has received funding from Merck Research Laboratories to study waning immunity to measles and mumps after immunization with the MMR-II® vaccine. This research has been reviewed by the Mayo Clinic Declaration of Competing Interest Review Board and was conducted in compliance with Mayo Clinic Declaration of Competing Interest policies. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Influenza A/H1N1 HAI titers pre- and post-vaccination. (A) Comparison of HAI titers at Baseline (Day 0) and Day 28 for the full cohort as well as younger and older subgroups, (B) Comparison of HAI titers between younger and older subgroups at Day 0 and Day 28, (C) Comparison of HAI titers in younger and older subgroups at Day 0 and Day 28 on the basis of biological sex.
FIGURE 2
FIGURE 2
Inflammasome-related caspase and cytokine secretion profiles in macrophages. Comparison of (A) caspase-1, (B) IL-18, (C) IL-1β, and (D) pro-IL-1β secretion in response to either R848 (a TLR7 agonist), influenza A/H1N1 virus, or a combination of both stimuli for subjects with sufficient cells for evaluation (n = 138). p-values derived from Wilcoxon’s signed-rank test.
FIGURE 3
FIGURE 3
Inflammasome-related gene expression in response to influenza stimulation. Volcano plot illustrating differentially expressed genes in monocyte-derived macrophages at Baseline in response to influenza A/H1N1 + R848 stimulation. Gene names highlighted for 40 genes with lowest p-values. Red indicates increased gene expression, blue indicates decreased gene expression.
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References

    1. Akagawa K. S., Komuro I., Kanazawa H., Yamazaki T., Mochida K., Kishi F. (2006). Functional Heterogeneity of colony-stimulating Factor-Induced Human Monocyte-Derived Macrophages. Respirology 11, (Suppl. l), S32–S36. 10.1111/j.1440-1843.2006.00805.x - DOI - PubMed
    1. Centers for Disease Control and Prevention (CDC) (2010). Estimates of Deaths Associated with Seasonal Influenza-United States, 1976-2007. Morbidity Mortality Weekly Rep. 59 (33), 1057–1062. - PubMed
    1. Chen W. H., Cross A. S., Edelman R., Sztein M. B., Blackwelder W. C., Pasetti M. F. (2011). Antibody and Th1-type Cell-Mediated Immune Responses in Elderly and Young Adults Immunized with the Standard or a High Dose Influenza Vaccine. Vaccine 29, 2865–2873. 10.1016/j.vaccine.2011.02.017 - DOI - PMC - PubMed
    1. Cox R. (2013). Correlates of protection to Influenza Virus, where Do We Go from Here?. Hum. Vaccin. Immunother. 9, 405–408. 10.4161/hv.22908 - DOI - PMC - PubMed
    1. Crooke S. N., Ovsyannikova I. G., Poland G. A., Kennedy R. B. (2019a). Immunosenescence and Human Vaccine Immune Responses. Immun. Ageing 16, 25. 10.1186/s12979-019-0164-9 - DOI - PMC - PubMed