Advanced Age Alters Monocyte and Macrophage Responses

Albright, Joslyn M.; Dunn, Robert C.; Shults, Jill A.; Boe, Devin M.; Afshar, Majid; Kovacs, Elizabeth J.

doi:10.1089/ars.2016.6691

Cited by 84 publications

(73 citation statements)

References 92 publications

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“…In addition to physical alterations of the lung structure, dysregulation of inflammation occurs as a result of aging and aging is the main risk factor for development of common nontransmissible lung diseases, including COPD, most forms of lung cancer and idiopathic pulmonary fibrosis (IPF), which most commonly affect people over 50 years of age. Inflamm‐aging describes the reduced ability of macrophages to perform their normal functions resulting in a chronic low grade inflammatory state in the elderly and downregulation of genes involved in cell cycle pathways . Mitochondrial dysfunction in structural cells and immune cells including macrophages results in pulmonary fibrosis .…”

Section: Origin and Maintenance Of Airway Macrophages Function In Lunmentioning

confidence: 99%

Airway macrophages as the guardians of tissue repair in the lung

2019

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The lungs present a challenging immunological dilemma for the host. Anatomically positioned at the environmental interface, they are constantly exposed to antigens, pollutants and microbes, while simultaneously facilitating vital gas exchange. Remarkably, the lungs maintain a functionally healthy state, ignoring harmless inhaled proteins, adapting to toxic environmental insults and limiting immune responses to allergens and pathogenic microbes. This functional strategy of environmental adaptation maintains immune defense, reduces tissue damage, and promotes and sustains lung immune tolerance. At steady state, airway macrophages produce low levels of cytokines, and suppress the induction of innate and adaptive immunity. These cells are primary initiators of lung innate immunity and possess high phagocytic activity to clear particulate antigens and apoptotic cell debris from the airways to regulate the response to infection and inflammation. In response to epithelial injury, resident and recruited macrophages drive tissue repair. In this review, we will focus on the functional importance of macrophages in tissue homeostasis and inflammation in the lung and highlight how environmental cues alter the plasticity and function of lung airway macrophages. We will also discuss mechanisms employed by pulmonary macrophages to promote resolution of tissue inflammation, and how and when this balance is perturbed, they contribute to pathological remodeling in acute and chronic infections and diseases such as asthma, idiopathic pulmonary fibrosis and chronic obstructive pulmonary disease.

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Section: Origin and Maintenance Of Airway Macrophages Function In Lunmentioning

confidence: 99%

Airway macrophages as the guardians of tissue repair in the lung

2019

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“…1). The initial response of macrophages to microbes and other inflammatory stimuli is reduced in aged hosts, which has been attributed to inflamm-ageing [45,72,[74][75][76][77]. This reduction in pathogen detection is probably a result of changes in TLR signalling pathways and constitutively elevated negative feedback signalling due to chronic inflammation present in older individuals [73].…”

Section: Ageing and Alveolar Macrophagesmentioning

confidence: 99%

Innate immune responses in the ageing lung

Boe

Boule

Kovacs

2016

Clinical and Experimental Immunology

116

103

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SummaryThe world is undergoing an unprecedented shift in demographics, with the number of individuals over the age of 60 years projected to reach 2 billion or more by 2050, representing 22% of the global population. Elderly people are at a higher risk for chronic disease and more susceptible to infection, due in part to age-related dysfunction of the immune system resulting from low-grade chronic inflammation known as 'inflamm-ageing'. The innate immune system of older individuals exhibits a diminished ability to respond to microbial threats and clear infections, resulting in a greater occurrence of many infectious diseases in elderly people. In particular, the incidence of and mortality from lung infections increase sharply with age, with such infections often leading to worse outcomes, prolonged hospital stays and life-threatening complications, such as sepsis or acute respiratory distress syndrome. In this review, we highlight research on bacterial pneumonias and pulmonary viral infections and discuss age-related changes in innate immunity that contribute to the higher rate of these infections in older populations. By understanding more clearly the innate immune defects in elderly individuals, we can design age-specific therapies to address lung infections in such a vulnerable population.

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“…Historically, this stimulus-induced shift in macrophage phenotype was referred to as M1 and M2 phenotypes with M1 being pro-inflammatory and M2 anti-inflammatory. 37,38 However, because of poor definition and inconsistencies in the cell surface markers defining these two phenotypes, a group of expert macrophage research investigators recently redefined macrophage classification terminology so that they are more narrowly classified based on the source of the macrophages and activation stimuli, as well as the specific group of markers associated with the particular activation phenotype 39 . Regardless of nomenclature, under resting conditions, alveolar macrophages maintain an anti-inflammatory profile to keep the pulmonary airway in check and are capable of rapidly springing into action, becoming strongly pro-inflammatory when alerted by the presence of foreign material (Figure 1).…”

Section: Innate Immune Cells Of the Lung And Changes With Advanced Agementioning

confidence: 99%

“…37 . In brief, both in vivo and in vitro studies conducted in humans and in various animal models suggest that many but not all of the functions of macrophages are slowed or diminished in magnitude in the aged, leaving the host unable to shift between phenotypes when needed 18,34,42 . Some of the better documented age-dependent changes in macrophage function are highlighted in Table 2.…”

Section: Innate Immune Cells Of the Lung And Changes With Advanced Agementioning

confidence: 99%

“…In contrast, in vitro stimulation of certain cell subsets, including blood monocytes, lung or peritoneal macrophages from aged subjects, yields lower levels of cytokines relative to cells from younger individuals, 46–48,93,94 suggesting either that monocyte/macrophages are not a major source of these mediators in vivo or that there are additional factors responsible for this discrepancy. The effects of aging on monocyte/macrophage functions were comprehensively reviewed elsewhere 42 .…”

Section: A Paradox: Aging Causes Higher Cytokine Levels In Vivo Yet mentioning

confidence: 99%

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Inflammaging and the Lung

Kovacs

Boe

Boule

et al. 2017

Clinics in Geriatric Medicine

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SYNOPSIS With the coming of the “Silver Tsunami,” expanding our knowledge about how a variety of intrinsic and extrinsic factors affect the immune system in the elderly is both timely and of immediate clinical need. It is clear that the global population is increasing in age. By the year 2030, over 20% of the population of the United States will be over 65 years of age. In this chapter, we will focus on how advanced age alters the immune systems and how this, in turn, modulates the ability of the aging lung to deal with the infectious challenges from both the outside world and from within the host.

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Advanced Age Alters Monocyte and Macrophage Responses

Abstract: In this article, there is a focus on the tissue-specific monocyte and macrophage subsets and how they are altered in the aged milieu, with the hope that this compilation of observations will spark an expansion of research in the field. Antioxid. Redox Signal. 25, 805-815.

Cited by 84 publications

References 92 publications

Airway macrophages as the guardians of tissue repair in the lung

Airway macrophages as the guardians of tissue repair in the lung

Innate immune responses in the ageing lung

Inflammaging and the Lung

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