Impaired phagocytic function in CX3CR1<sup>+</sup> tissue‐resident skeletal muscle macrophages prevents muscle recovery after influenza A virus‐induced pneumonia in old mice

Runyan, Constance E.; Welch, Lynn C.; Lecuona, Emilia; Shigemura, Masahiko; Amarelle, Luciano; Abdala‐Valencia, Hiam; Joshi, Nikita; Lu, Ziyan; Nam, Ki-Won; Markov, Nikolay S.; McQuattie‐Pimentel, Alexandra C.; Piseaux‐Aillon, Raul; Politanska, Yuliya; Sichizya, Lango; Watanabe, Satoshi; Williams, Kibileri; Budinger, G. R. Scott; Sznajder, Jacob I.; Misharin, Alexander V.

doi:10.1111/acel.13180

Cited by 25 publications

(18 citation statements)

References 71 publications

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“…GM-CSF also plays an important role in the host response to influenza A infection; transgenic expression of Csf2 in mice accelerates viral clearance and attenuates lung injury after influenza A infection, and genetic loss of Csf2 results in more severe lung injury (25)(26)(27). In a murine model of influenza A pneumonia, we reported that, although viral clearance was similar in young adult and aged mice, older mice showed enhanced mortality and worsened lung injury when compared with young adult mice (28). We found that GM-CSF administered intratracheally to mice 1 day before influenza A infection reduced mortality in both young and aged mice (Figure 5, A and B, and Supplemental Figure 5, A and B).…”

Section: Resultsmentioning

confidence: 94%

The lung microenvironment shapes a dysfunctional response of alveolar macrophages in aging

McQuattie‐Pimentel¹,

Ren²,

Joshi³

et al. 2021

Journal of Clinical Investigation

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105

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Alveolar macrophages orchestrate the response to viral infections. Age-related changes in these cells may underlie the differential severity of pneumonia in older patients. We performed an integrated analysis of single-cell RNA-Seq data that revealed homogenous age-related changes in the alveolar macrophage transcriptome in humans and mice. Using genetic lineage tracing with sequential injury, heterochronic adoptive transfer, and parabiosis, we found that the lung microenvironment drove an age-related resistance of alveolar macrophages to proliferation that persisted during influenza A viral infection. Ligand-receptor pair analysis localized these changes to the extracellular matrix, where hyaluronan was increased in aged animals and altered the proliferative response of bone marrow-derived macrophages to granulocyte macrophage colony-stimulating factor (GM-CSF). Our findings suggest that strategies targeting the aging lung microenvironment will be necessary to restore alveolar macrophage function in aging.

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Section: Resultsmentioning

confidence: 94%

The lung microenvironment shapes a dysfunctional response of alveolar macrophages in aging

McQuattie‐Pimentel¹,

Ren²,

Joshi³

et al. 2021

Journal of Clinical Investigation

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105

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“…All tissues and cells were immediately frozen on dry ice and stored at −80 °C for processing. Muscle satellite cells were prepared as described in work by Runyan et al 74 .…”

Section: Statistics and Reproducibilitymentioning

confidence: 99%

Aging is associated with a systemic length-associated transcriptome imbalance

et al. 2022

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Aging is among the most important risk factors for morbidity and mortality. To contribute toward a molecular understanding of aging, we analyzed age-resolved transcriptomic data from multiple studies. Here, we show that transcript length alone explains most transcriptional changes observed with aging in mice and humans. We present three lines of evidence supporting the biological importance of the uncovered transcriptome imbalance. First, in vertebrates the length association primarily displays a lower relative abundance of long transcripts in aging. Second, eight antiaging interventions of the Interventions Testing Program of the National Institute on Aging can counter this length association. Third, we find that in humans and mice the genes with the longest transcripts enrich for genes reported to extend lifespan, whereas those with the shortest transcripts enrich for genes reported to shorten lifespan. Our study opens fundamental questions on aging and the organization of transcriptomes.

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“…Another recently described systemic effect of CX3CR1 is dead cell disposal. An experiment addressing muscle cell death induced by influenza virus infection demonstrates that CX3CR1+ cells are required for phagocytic disposal (Runyan et al 2020). Similarly, phagocytic disposal was impaired in 20-24 months old aged mice.…”

Section: Systemic Cx3cr1 + Effects With Potential Impact On Kidney Diseasementioning

confidence: 99%

Regulation and function of CX3CR1 and its ligand CX3CL1 in kidney disease

Vietinghoff¹,

Kurts²

2021

Cell Tissue Res

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Attraction, retention, and differentiation of leukocytes to and within the kidney are governed by chemokines. The chemokine CX3CL1 (fractalkine) and its receptor CX3CR1 are exemplary in this regard as they are highly expressed and further upregulated in a range of kidney diseases. CX3CL1 is chiefly produced by renal endothelium and tubular epithelium, where it promotes leukocyte attraction. Recent data suggest that in addition to established soluble mediators, cellular interactions may enhance CX3CL1 expression. The receptor CX3CR1 is essential in myeloid phagocyte homing to the kidney at homeostasis, after acute cell depletion and in inflammation. CX3CR1 and its ligand are highly regulated in human kidney diseases such as IgA nephritis, systemic lupus erythematosus, and inflammatory conditions such as transplant rejection. A mechanistic role of CX3CR1 has been established in experimental models of nephrotoxic nephritis and renal candidiasis. It is debated in fibrosis. Recent publications demonstrate a role for CX3CR1+ myeloid cells in radio-contrast-agent and sepsis-induced kidney damage. Systemically, circulating CX3CR1+ monocytes reversibly increase in individuals with renal impairment and correlate with their cardiovascular risk. In this review, we discuss role and regulatory mechanisms of the CX3CL1-CX3CR1 axis in both localized and systemic effects of renal inflammation.

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Impaired phagocytic function in CX3CR1⁺ tissue‐resident skeletal muscle macrophages prevents muscle recovery after influenza A virus‐induced pneumonia in old mice

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 25 publications

References 71 publications

The lung microenvironment shapes a dysfunctional response of alveolar macrophages in aging

The lung microenvironment shapes a dysfunctional response of alveolar macrophages in aging

Aging is associated with a systemic length-associated transcriptome imbalance

Regulation and function of CX3CR1 and its ligand CX3CL1 in kidney disease

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Impaired phagocytic function in CX3CR1+ tissue‐resident skeletal muscle macrophages prevents muscle recovery after influenza A virus‐induced pneumonia in old mice

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 25 publications

References 71 publications

The lung microenvironment shapes a dysfunctional response of alveolar macrophages in aging

The lung microenvironment shapes a dysfunctional response of alveolar macrophages in aging

Aging is associated with a systemic length-associated transcriptome imbalance

Regulation and function of CX3CR1 and its ligand CX3CL1 in kidney disease

Contact Info

Product

Resources

About

Impaired phagocytic function in CX3CR1⁺ tissue‐resident skeletal muscle macrophages prevents muscle recovery after influenza A virus‐induced pneumonia in old mice