Aged neutrophils accumulate in lymphoid tissues from healthy elderly mice and infiltrate T- and B-cell zones

Federica Tomay, Kelsi Wells, Lelinh Duong, Jean Wei Tsu, Danielle E. Dye, Hannah Radley-Crabb, Miranda D. Grounds, Tea Shavlakadze, Pat Metharom, Delia J. Nelson, Connie Jackaman

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

The average age of the human population is rising, leading to an increasing burden of age-related diseases, including increased susceptibility to infection. However, immune function can decrease with age which could impact on processes that require a functional immune system. Aging is also characterized by chronic low-grade inflammation which could further impact immune cell function. While changes to neutrophils in blood during aging have been described, little is known in aging lymphoid organs. This study used female C57BL/6J mice comparing bone marrow (BM), spleen and lymph nodes from young mice aged 2-3 months (equivalent to 18 human years) with healthy elderly mice aged 22-24 months (equivalent to 60-70 human years). Neutrophil proportions increased in BM and secondary lymphoid organs of elderly mice relative to their younger counterparts and presented an atypical phenotype. Interestingly, neutrophils from elderly spleen and lymph nodes were long lived (with decreased apoptosis via Annexin V staining and increased proportion of BrdUneg mature cells) with splenic neutrophils also demonstrating a hypersegmented morphology. Furthermore, splenic neutrophils of elderly mice expressed a mixed phenotype with increased expression of activation markers, CD11b and ICAM-1, increased proinflammatory TNFα, yet increased anti-inflammatory transforming growth factor-beta. Elderly splenic architecture was compromised, as the marginal zone (required for clearing infections) was contracted. Moreover, neutrophils from elderly but not young mice accumulated in lymph node and splenic T- and B-cell zones. Overall, the expansion of functionally compromised neutrophils could contribute to increased susceptibility to infection observed in the elderly.

Original languageEnglish
JournalImmunology and Cell Biology
DOIs
Publication statusE-pub ahead of print - 30 Mar 2018

Fingerprint

Lymphoid Tissue
Neutrophils
B-Lymphocytes
Lymph Nodes
Spleen
Infection
Bone Marrow
Phenotype
Annexin A5
Intercellular Adhesion Molecule-1
Inbred C57BL Mouse
Transforming Growth Factor beta
Immune System
Anti-Inflammatory Agents
Apoptosis
Staining and Labeling
Inflammation
Population

Cite this

Tomay, Federica ; Wells, Kelsi ; Duong, Lelinh ; Tsu, Jean Wei ; Dye, Danielle E. ; Radley-Crabb, Hannah ; Grounds, Miranda D. ; Shavlakadze, Tea ; Metharom, Pat ; Nelson, Delia J. ; Jackaman, Connie. / Aged neutrophils accumulate in lymphoid tissues from healthy elderly mice and infiltrate T- and B-cell zones. In: Immunology and Cell Biology. 2018.
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abstract = "The average age of the human population is rising, leading to an increasing burden of age-related diseases, including increased susceptibility to infection. However, immune function can decrease with age which could impact on processes that require a functional immune system. Aging is also characterized by chronic low-grade inflammation which could further impact immune cell function. While changes to neutrophils in blood during aging have been described, little is known in aging lymphoid organs. This study used female C57BL/6J mice comparing bone marrow (BM), spleen and lymph nodes from young mice aged 2-3 months (equivalent to 18 human years) with healthy elderly mice aged 22-24 months (equivalent to 60-70 human years). Neutrophil proportions increased in BM and secondary lymphoid organs of elderly mice relative to their younger counterparts and presented an atypical phenotype. Interestingly, neutrophils from elderly spleen and lymph nodes were long lived (with decreased apoptosis via Annexin V staining and increased proportion of BrdUneg mature cells) with splenic neutrophils also demonstrating a hypersegmented morphology. Furthermore, splenic neutrophils of elderly mice expressed a mixed phenotype with increased expression of activation markers, CD11b and ICAM-1, increased proinflammatory TNFα, yet increased anti-inflammatory transforming growth factor-beta. Elderly splenic architecture was compromised, as the marginal zone (required for clearing infections) was contracted. Moreover, neutrophils from elderly but not young mice accumulated in lymph node and splenic T- and B-cell zones. Overall, the expansion of functionally compromised neutrophils could contribute to increased susceptibility to infection observed in the elderly.",
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Aged neutrophils accumulate in lymphoid tissues from healthy elderly mice and infiltrate T- and B-cell zones. / Tomay, Federica; Wells, Kelsi; Duong, Lelinh; Tsu, Jean Wei; Dye, Danielle E.; Radley-Crabb, Hannah; Grounds, Miranda D.; Shavlakadze, Tea; Metharom, Pat; Nelson, Delia J.; Jackaman, Connie.

In: Immunology and Cell Biology, 30.03.2018.

Research output: Contribution to journalArticle

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AU - Tomay, Federica

AU - Wells, Kelsi

AU - Duong, Lelinh

AU - Tsu, Jean Wei

AU - Dye, Danielle E.

AU - Radley-Crabb, Hannah

AU - Grounds, Miranda D.

AU - Shavlakadze, Tea

AU - Metharom, Pat

AU - Nelson, Delia J.

AU - Jackaman, Connie

PY - 2018/3/30

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N2 - The average age of the human population is rising, leading to an increasing burden of age-related diseases, including increased susceptibility to infection. However, immune function can decrease with age which could impact on processes that require a functional immune system. Aging is also characterized by chronic low-grade inflammation which could further impact immune cell function. While changes to neutrophils in blood during aging have been described, little is known in aging lymphoid organs. This study used female C57BL/6J mice comparing bone marrow (BM), spleen and lymph nodes from young mice aged 2-3 months (equivalent to 18 human years) with healthy elderly mice aged 22-24 months (equivalent to 60-70 human years). Neutrophil proportions increased in BM and secondary lymphoid organs of elderly mice relative to their younger counterparts and presented an atypical phenotype. Interestingly, neutrophils from elderly spleen and lymph nodes were long lived (with decreased apoptosis via Annexin V staining and increased proportion of BrdUneg mature cells) with splenic neutrophils also demonstrating a hypersegmented morphology. Furthermore, splenic neutrophils of elderly mice expressed a mixed phenotype with increased expression of activation markers, CD11b and ICAM-1, increased proinflammatory TNFα, yet increased anti-inflammatory transforming growth factor-beta. Elderly splenic architecture was compromised, as the marginal zone (required for clearing infections) was contracted. Moreover, neutrophils from elderly but not young mice accumulated in lymph node and splenic T- and B-cell zones. Overall, the expansion of functionally compromised neutrophils could contribute to increased susceptibility to infection observed in the elderly.

AB - The average age of the human population is rising, leading to an increasing burden of age-related diseases, including increased susceptibility to infection. However, immune function can decrease with age which could impact on processes that require a functional immune system. Aging is also characterized by chronic low-grade inflammation which could further impact immune cell function. While changes to neutrophils in blood during aging have been described, little is known in aging lymphoid organs. This study used female C57BL/6J mice comparing bone marrow (BM), spleen and lymph nodes from young mice aged 2-3 months (equivalent to 18 human years) with healthy elderly mice aged 22-24 months (equivalent to 60-70 human years). Neutrophil proportions increased in BM and secondary lymphoid organs of elderly mice relative to their younger counterparts and presented an atypical phenotype. Interestingly, neutrophils from elderly spleen and lymph nodes were long lived (with decreased apoptosis via Annexin V staining and increased proportion of BrdUneg mature cells) with splenic neutrophils also demonstrating a hypersegmented morphology. Furthermore, splenic neutrophils of elderly mice expressed a mixed phenotype with increased expression of activation markers, CD11b and ICAM-1, increased proinflammatory TNFα, yet increased anti-inflammatory transforming growth factor-beta. Elderly splenic architecture was compromised, as the marginal zone (required for clearing infections) was contracted. Moreover, neutrophils from elderly but not young mice accumulated in lymph node and splenic T- and B-cell zones. Overall, the expansion of functionally compromised neutrophils could contribute to increased susceptibility to infection observed in the elderly.

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