Reduced bioenergetics and toll-like receptor 1 function in human polymorphonuclear leukocytes in aging

Qian, Feng; Guo, Ximing; Wang, Xiaomei; Yuan, Xiaoling; Chen, Shu; Malawista, Stephen E.; Bockenstedt, Linda K.; Allore, Heather; Montgomery, Ruth R.

doi:10.18632/aging.100642

Cited by 47 publications

(49 citation statements)

References 49 publications

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“…Historically, authors have previously argued that age-related immune dysfunction could be due to an exacerbated response in the acute time period to both infectious and non-infectious inflammation (4, 6). However, there has been a shift in the more current literature regarding aging immune dysfunction (7–9, 39). After intra-abdominal sepsis, the cytokine response of aged mice, as compared to young mice, was found to be similar when comparing models with similar mortality among the cohorts (5).…”

Section: Discussionmentioning

confidence: 99%

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A Detailed Characterization of the Dysfunctional Immunity and Abnormal Myelopoiesis Induced by Severe Shock and Trauma in the Aged

Nacionales

Szpila

Ungaro

et al. 2015

The Journal of Immunology

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The elderly are particularly susceptible to trauma, and their outcomes are frequently dismal. Such patients often have complicated clinical courses and ultimately die from infection and sepsis. Recent research has revealed that although elderly subjects have increased baseline inflammation as compared to their younger counterparts, the elderly do not respond to severe infection/injury with an exaggerated inflammatory response. Initial retrospective analysis of clinical data from the Glue Grant trauma database demonstrated that despite a similar frequency, elderly trauma patients have worse outcomes to pneumonia than younger subjects. Subsequent analysis with a murine trauma model also demonstrated that elderly mice had increased mortality after post-trauma Pseudomonas pneumonia. Blood, bone marrow, and bronchoalveolar lavage sample analyses from juvenile and 20–24 month old mice showed that increased mortality to trauma combined with secondary infection in the aged are not due to an exaggerated inflammatory response. Rather, they are due to a failure of bone marrow progenitors, blood neutrophils, and bronchoalveolar lavage cells to initiate and complete an ‘emergency myelopoietic’ response, engendering myeloid cells that fail to clear secondary infection. In addition, the elderly appeared unable to effectively resolve their inflammatory response to severe injury.

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Section: Discussionmentioning

confidence: 99%

“…Authors have previously argued that age-related immune dysfunction is due to an acute exacerbated response to both infectious and non-infectious inflammation (4–6). However, more recent analysis appears to refute these claims (2, 7–9). …”

Section: Introductionmentioning

confidence: 99%

A Detailed Characterization of the Dysfunctional Immunity and Abnormal Myelopoiesis Induced by Severe Shock and Trauma in the Aged

Nacionales

Szpila

Ungaro

et al. 2015

The Journal of Immunology

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show abstract

“…Prominent affected pathways are the MAP kinases, the Jak/STAT and the PI3K-Akt pathways, which are important regulators of neutrophil functions. 21,22 The decline of signal transduction in these pathways contributes to age-associated neutrophil dysfunction such as directional chemotaxis. Moreover, neutrophils in older adults have reduced bioenergetics, and lower expression of TLR1, leading to impairment of various neutrophil functions, including activation of integrins (CD18 and CD11b), and production of IL-8.…”

Section: Effects Of Aging On Innate Immune Responses To Wnv Infectionmentioning

confidence: 99%

“…Moreover, neutrophils in older adults have reduced bioenergetics, and lower expression of TLR1, leading to impairment of various neutrophil functions, including activation of integrins (CD18 and CD11b), and production of IL-8. 22 …”

Section: Effects Of Aging On Innate Immune Responses To Wnv Infectionmentioning

confidence: 99%

Role of Immune Aging in Susceptibility to West Nile Virus

Yao

Montgomery

2016

Methods in Molecular Biology

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“…Studies in human and animal models across cell type, activation state, and tissue context demonstrate altered expression and functional efficiency of TLRs and downstream signalling events that lead to dysregulation of immune responses in aging [3]. In human neutrophils and monocytes, decreased surface expression of TLR1 has been associated with diminished TLR1/TLR2-induced cytokine production and vaccine responsiveness [9–11]. TLR-dependent expression of the costimulatory molecules CD80 and CD86 in vitro was altered in monocytes from older adults [12].…”

Section: Effects Of Aging On Pattern Recognition Receptors (Prrs)mentioning

confidence: 99%

Effect of aging on microRNAs and regulation of pathogen recognition receptors

Olivieri

Procopio

Montgomery

2014

Current Opinion in Immunology

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Immunosenescence is the multifactorial age-associated immune deteriorization that leads to increased susceptibility to infections and decreased responses to vaccines. Recent studies have shown a fundamental role for microRNAs (miRNAs) in regulating immune responses, and nearly all the miRNAs involved in immune regulation show modulation during aging. Aging-associated miRNAs are largely negative regulators of the immune innate response and target central nodes of aging-associated networks, in particular, NF-κB, the downstream effector of TLR signals that leads to induction of proinflammatory responses. Multiple miRNAs have been reported to share similar regulatory activity. Here we review miRNA regulation of human innate immune recognition in aging, including both activation and resolution of inflammation, critical issues in detection, and areas of active investigation into our understanding of immunosenescence.

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Reduced bioenergetics and toll-like receptor 1 function in human polymorphonuclear leukocytes in aging

Cited by 47 publications

References 49 publications

A Detailed Characterization of the Dysfunctional Immunity and Abnormal Myelopoiesis Induced by Severe Shock and Trauma in the Aged

A Detailed Characterization of the Dysfunctional Immunity and Abnormal Myelopoiesis Induced by Severe Shock and Trauma in the Aged

Role of Immune Aging in Susceptibility to West Nile Virus

Effect of aging on microRNAs and regulation of pathogen recognition receptors

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