Macrophages and the Recovery from Acute and Chronic Inflammation

Hamidzadeh, Kajal; Christensen, Stephen M; Dalby, Elizabeth; Chandrasekaran, Prabha; Mosser, David M.

doi:10.1146/annurev-physiol-022516-034348

Cited by 286 publications

(215 citation statements)

References 183 publications

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“…Although the microglial inflammatory response is acutely initiated to neutralize harm and to promote tissue repair and functional recovery, the sustained activation of the inflammatory reaction due to unresolved damage is associated with loss of CNS homeostasis and neurotoxicity [134]. As such, innate immunity mediated inflammation is a tightly regulated process at different cellular levels, including ligand binding, signal transduction, transcription, and epigenetics, whose outcome ultimately depends on context-associated balance of pro- and anti-inflammatory cytokines as well as other inflammatory mediators [135]. Notably, proteolytic pathways such as the ubiquitin-proteasome system also contribute to the regulation of inflammation [135,136].…”

Section: Autophagy and Microglial Inflammationmentioning

confidence: 99%

“…As such, innate immunity mediated inflammation is a tightly regulated process at different cellular levels, including ligand binding, signal transduction, transcription, and epigenetics, whose outcome ultimately depends on context-associated balance of pro- and anti-inflammatory cytokines as well as other inflammatory mediators [135]. Notably, proteolytic pathways such as the ubiquitin-proteasome system also contribute to the regulation of inflammation [135,136]. In agreement, recent work indicates that autophagy controls the inflammatory response in innate immune macrophages [16,137] and microglia [138].…”

Section: Autophagy and Microglial Inflammationmentioning

confidence: 99%

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Autophagy and Microglia: Novel Partners in Neurodegeneration and Aging

Plaza-Zabala

Sierra-Torre

Sierra

2017

IJMS

260

210

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Abstract:Autophagy is emerging as a core regulator of Central Nervous System (CNS) aging and neurodegeneration. In the brain, it has mostly been studied in neurons, where the delivery of toxic molecules and organelles to the lysosome by autophagy is crucial for neuronal health and survival. However, we propose that the (dys)regulation of autophagy in microglia also affects innate immune functions such as phagocytosis and inflammation, which in turn contribute to the pathophysiology of aging and neurodegenerative diseases. Herein, we first describe the basic concepts of autophagy and its regulation, discuss key aspects for its accurate monitoring at the experimental level, and summarize the evidence linking autophagy impairment to CNS senescence and disease. We focus on acute, chronic, and autoimmunity-mediated neurodegeneration, including ischemia/stroke, Alzheimer's, Parkinson's, and Huntington's diseases, and multiple sclerosis. Next, we describe the actual and potential impact of autophagy on microglial phagocytic and inflammatory function. Thus, we provide evidence of how autophagy may affect microglial phagocytosis of apoptotic cells, amyloid-β, synaptic material, and myelin debris, and regulate the progression of age-associated neurodegenerative diseases. We also discuss data linking autophagy to the regulation of the microglial inflammatory phenotype, which is known to contribute to age-related brain dysfunction. Overall, we update the current knowledge of autophagy and microglia, and highlight as yet unexplored mechanisms whereby autophagy in microglia may contribute to CNS disease and senescence.

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Section: Autophagy and Microglial Inflammationmentioning

confidence: 99%

Section: Autophagy and Microglial Inflammationmentioning

confidence: 99%

Autophagy and Microglia: Novel Partners in Neurodegeneration and Aging

Plaza-Zabala

Sierra-Torre

Sierra

2017

IJMS

260

210

View full text Add to dashboard Cite

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“…IFN‐γ activates macrophages and is secreted in response to stimuli such as viral, bacterial pathogens. Binding of IFN‐γ induces heightened release of macrophage inflammatory cytokines such as TNF‐α primarily through STAT1 activation . Consistent with an increase in IFN‐γ secretion, TNF‐α levels were also increased when macrophages were exposed to S. aureus .…”

Section: Discussionmentioning

confidence: 73%

“…Canine macrophages exhibited a similar trend when co-cultured with OS and S. aureus: rophage inflammatory cytokines such as TNF-α primarily through STAT1 activation. 25 Consistent with an increase in IFN-γ secretion, TNF-α levels were also increased when macrophages were exposed to S. aureus. TNF-α is one of the dominant cytokines in an inflammatory response to LPS and other bacterial products.…”

Section: Discussionmentioning

confidence: 77%

Immune dysregulation and osteosarcoma: Staphylococcus aureus downregulates TGF‐β and heightens the inflammatory signature in human and canine macrophages suppressed by osteosarcoma

Tuohy

Somarelli

Borst

et al. 2019

Vet Comparative Oncology

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Since William Coley utilized bacterial immunotherapy to treat sarcomas in the late 19th century, an association between infection and improved survival has been reported for human and canine osteosarcoma patients. One of the reasons for this improved survival is likely a reactivation of the host immune system towards an inflammatory anti‐tumour response, and one of the key players is the macrophage. Yet, despite their importance, the response of macrophages to infectious agents in the context of osteosarcoma has not been thoroughly evaluated. The aim of this study was to evaluate how in vitro exposure to a bacterial agent (Staphylococcus aureus) influenced canine and human macrophage differentiation in the presence of osteosarcoma. Our hypothesis was that S. aureus would, in the presence of osteosarcoma, induce a macrophage phenotype with significantly increased inflammatory signatures. Consistent with our hypothesis, human macrophages co‐cultured with osteosarcoma and S. aureus exhibited increased IFN‐γ, TNF‐α and IL‐12p70 cytokine secretion, decreased TGF‐β cytokine secretion and increased mRNA expression of TNF‐α when compared with macrophages co‐cultured with osteosarcoma and to macrophages cultured alone. Canine macrophages similarly exhibited increased IFN‐γ and TNF‐α cytokine secretion, decreased TGF‐β cytokine secretion, increased mRNA expression of TNF‐α and increased surface receptor expression of CD80 when co‐cultured with osteosarcoma and S. aureus. Collectively, the findings of this study suggest that infection upregulates the inflammatory immune response to counteract osteosarcoma‐induced immune suppression. This work informs a potential therapeutic strategy to optimize inflammatory stimuli for triggering an anti‐osteosarcoma macrophage response.

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“…However, more recent studies reported that M2a and M2c macrophages also exist in degenerative IVD and may contribute to IVD pathology . They are increased following tissue inflammation and their phenotypes change depending on the time of injury . However, the mechanism underlying the mobilization of macrophages to injured IVDs is not well‐understood.…”

mentioning

confidence: 99%

Sequential CCL2 Expression Profile After Disc Injury in Mice

Nakawaki

Uchida

Miyagi

et al. 2019

Journal Orthopaedic Research

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Macrophages produce proinflammatory cytokines in injured intervertebral discs (IVDs). We recently showed that macrophage‐derived inflammatory cytokines contribute to the production of pain‐related factors. However, the mechanism by which macrophages are recruited to injured IVDs has not been fully clarified. Here, we examined the expression dynamics of the chemokine CCL2 in a mouse IVD injury model and the mechanisms of its regulation. The percentage of macrophages increased from day 1 after injury and persisted up until day 28. At 1 and 3 days after injury, the expression of both Ccl2 messenger RNA (mRNA) and CCL2 protein was elevated in the IVD injury group, after which expression decreased to basal levels. Consistent with the increase in CCL2 expression, Ccr2 and Tnfa expression and various types of macrophages were also immediately elevated following disc injury. Further, tumor necrosis factor‐α (TNF‐α) stimulated Ccl2 mRNA and CCL2 protein expression in IVD cells in vitro. The expressions of M1 (Cd86 and Nos2) and M2a (Ym1) macrophage markers were all significantly elevated from day 1 following injury in injured compared with control mice. Meanwhile, the expression of Cd206 (M2a and M2c marker) was significantly elevated on days 3, 7, 14, and 28 following injury. These results suggest that in IVD injury, TNF‐α stimulates CCL2, which, in turn, mediates the recruitment of macrophages with the recruited macrophages subsequently differentiating into M1 and M2 subtypes. CCL2 signaling may, therefore, play an important role in IVD pathology via macrophage recruitment. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:895‐901, 2020

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Macrophages and the Recovery from Acute and Chronic Inflammation

Cited by 286 publications

References 183 publications

Autophagy and Microglia: Novel Partners in Neurodegeneration and Aging

Autophagy and Microglia: Novel Partners in Neurodegeneration and Aging

Immune dysregulation and osteosarcoma: Staphylococcus aureus downregulates TGF‐β and heightens the inflammatory signature in human and canine macrophages suppressed by osteosarcoma

Sequential CCL2 Expression Profile After Disc Injury in Mice

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