Aging of the innate immune system

Shaw, Albert C.; Joshi, Samit R; Greenwood, Hannah; Panda, Alexander; Lord, Janet M.

doi:10.1016/j.coi.2010.05.003

Cited by 553 publications

(445 citation statements)

References 55 publications

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“…Such low‐grade innate immune activation and inflammatory shift of the microenvironment, coined “inflammaging” (Franceschi et al, 2007), has been reported for several different organ systems (Shaw, Joshi, Greenwood, Panda, & Lord, 2010). Its impact on peripheral nerve maintenance and regeneration remains unknown, thus precluding mechanistic investigation.…”

Section: Discussionmentioning

confidence: 99%

Inflammaging impairs peripheral nerve maintenance and regeneration

et al. 2018

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The regenerative capacity of peripheral nerves declines during aging, contributing to the development of neuropathies, limiting organism function. Changes in Schwann cells prompt failures in instructing maintenance and regeneration of aging nerves; molecular mechanisms of which have yet to be delineated. Here, we identified an altered inflammatory environment leading to a defective Schwann cell response, as an underlying mechanism of impaired nerve regeneration during aging. Chronic inflammation was detected in intact uninjured old nerves, characterized by increased macrophage infiltration and raised levels of monocyte chemoattractant protein 1 (MCP1) and CC chemokine ligand 11 (CCL11). Schwann cells in the old nerves appeared partially dedifferentiated, accompanied by an activated repair program independent of injury. Upon sciatic nerve injury, an initial delayed immune response was followed by a persistent hyperinflammatory state accompanied by a diminished repair process. As a contributing factor to nerve aging, we showed that CCL11 interfered with Schwann cell differentiation in vitro and in vivo. Our results indicate that increased infiltration of macrophages and inflammatory signals diminish regenerative capacity of aging nerves by altering Schwann cell behavior. The study identifies CCL11 as a promising target for anti‐inflammatory therapies aiming to improve nerve regeneration in old age.

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Section: Discussionmentioning

confidence: 99%

Inflammaging impairs peripheral nerve maintenance and regeneration

et al. 2018

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“…In rodents many data exist showing macrophage functional changes with aging, however much less is known regarding changes in humans [3,7,8,45,46]. Nevertheless, data suggest that monocyte/macrophages from aged individuals display age-related dysfunction [47][48][49].…”

Section: Monocyte/macrophages Functional Changes With Agingmentioning

confidence: 99%

“…Nevertheless, data suggest that monocyte/macrophages from aged individuals display age-related dysfunction [47][48][49]. These alterations include a decrease of cell surface TLRs expression (TLR1 and TLR4) though this finding has not been unequivocally demonstrated [3,7,48,50]. In addition TLR signalling pathways show age-related alterations [29] and this has been linked to altered chemotaxis as shown by the reduced number of infiltrating macrophages in wounds of elderly humans [51,52].…”

Section: Monocyte/macrophages Functional Changes With Agingmentioning

confidence: 99%

“…The attention of immunologists has focused on T lymphocyte dysregulation with age as their alterations were considered as the hallmark of immunosenescence [3,6]. Accumulating evidence now suggests that immunosenescence is not only restricted to the adaptive but also affects the innate immune system [7,8]. Furthermore, it is clear that the sustained function of innate cells is indispensable for the adequate functioning of the adaptive immune response [9].…”

Section: Introductionmentioning

confidence: 99%

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The Innate Immune System and Aging: What is the Contribution to Immunosenescence ?

Fülöp

Fortin²,

Lesur³

et al. 2012

TOLSJ

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Abstract:The immune system plays an important role in the defence against various threats to health, such as pathogens, cancer cells or modified-self proteins. With aging there is a decrease in the immune response, called immunosenescence, concomitantly with the increase in some age-related diseases such as infections, autoimmune disorders, chronic inflammatory diseases and cancer. The immune response is traditionally divided between innate and adaptive immune responses. Accumulating evidence suggests that immunosenescence is not only restricted to the adaptive but also affects the innate immune system. Assessment of innate immune system functions revealed that it is also susceptible to age-related dysregulation. Furthermore, it is becoming clear that the sustained function of innate cells is indispensable for the adequate functioning of the adaptive immune response. This review will describe the changes in the innate immune response with aging and the recent discoveries, which may shed new light on its contribution to immunosenescence.

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“…2,3 The innate immune system mount an efficient antiviral response in the early life, which includes monocytes, phagocytes, natural killer (NK) cells, Vc9Vd2-T cells and other recognition and effector elements. 4 NK cells are key effector cells in the innate immunity, which play a critical role in the first line of host defense against acute viral infections by directly killing infected cells and inhibiting virus replication through secretion of antiviral cytokines. 5,6 NK cells are broadly reactive against different kinds of virus, such as influenza virus, herpes viruses, hepatitis B virus and Marburg virus, indicating a general role of the cells in antiviral immune responses.…”

Section: Introductionmentioning

confidence: 99%

Impaired NK cell antiviral cytokine response against influenza virus in small-for-gestational-age neonates

Mao

et al. 2013

Cell Mol Immunol

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The neonates, particularly small-for-gestational-age (SGA) ones, are susceptible to various microbial infections. Natural killer (NK) cells are critical components of host innate immunity system and the main source of the inflammatory cytokines, which provide critical protection during the early phase of viral infections before the development of an appropriate adaptive immune response. However, little is known about the antiviral effects of NK cells in neonates especially the SGA population. Herein, a prospective descriptive study was performed to determine the differences of NK cell immunity among adults, appropriate-for gestational-age (AGA) and SGA neonates. Adults have much higher NK cell number in peripheral blood than that in cord blood from neonates. In response to influenza virus stimulation, neonatal NK cells, especially SGA baby cells, expressed significantly lower antiviral cytokines including perforin, interferon (IFN)-c and tumor-necrosis factor (TNF)-a responses than adult NK cells. In addition, the antiviral cytokine responses of NK cells were positively correlated with neonatal birth weight. Our data suggested that the depressed antiviral activity and less frequency of NK cells are likely to be responsible for the high susceptibility to microbial infection in neonates, at least in part. Improving the function of innate immunity may provide a new way to defend virus infection.

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Aging of the innate immune system

Cited by 553 publications

References 55 publications

Inflammaging impairs peripheral nerve maintenance and regeneration

Inflammaging impairs peripheral nerve maintenance and regeneration

The Innate Immune System and Aging: What is the Contribution to Immunosenescence ?

Impaired NK cell antiviral cytokine response against influenza virus in small-for-gestational-age neonates

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