Peripherally-sourced myeloid antigen presenting cells increase with advanced aging

Honarpisheh, Pedram; Blixt, Frank W; Conesa, Maria P. Blasco; Won, William W.; d’Aigle, John; Munshi, Yashasvee; Hudobenko, Jacob; Furr, J. Weldon; Mobley, Alexis S; Lee, M.S. Juneyoung; Brannick, Katherine E.; Zhu, Manlian; Hazen, Amy L.; Bryan, Robert M.; McCullough, Louise D.; Ganesh, Bhanu Priya

doi:10.1016/j.bbi.2020.08.023

Cited by 16 publications

(14 citation statements)

References 86 publications

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“…Consistent with reported increased proliferation and tissue-redistribution of myeloid cells with aging, we have shown that peripherally sourced APCs significantly increase in the brain with advancing age. 114 This myelocytic accumulation in the brain positively correlated with age-related changes in the gut microbiota (decreased Akkermansia ) and behavioral deficits. 114 Although the proportion of neutrophils in circulation does not seem to be affected, their functions (chemotaxis, phagocytosis, production of reactive oxygen species [ROS]) are impaired with aging.…”

Section: Aging and The Mgbamentioning

confidence: 93%

“…114 This myelocytic accumulation in the brain positively correlated with age-related changes in the gut microbiota (decreased Akkermansia ) and behavioral deficits. 114 Although the proportion of neutrophils in circulation does not seem to be affected, their functions (chemotaxis, phagocytosis, production of reactive oxygen species [ROS]) are impaired with aging. 101,115 The microbiota drives neutrophil aging via TLR and MyD88 signaling, and depletion of the microbiota (in GF or antibiotic-treated mice) reduced the number of circulating aged neutrophils (CXCR4 high CD62L low ) and improved survival in animal models of endotoxin-induced septic shock.…”

Section: Aging and The Mgbamentioning

confidence: 93%

“…179 The prestroke number of brain APCs is significantly higher in aged mice, and is correlated with specific age-related shifts in the microbiota (eg, abundance of Akkermansia is negatively correlated with number of brain APCs). 114 The poststroke composition of infiltrating myeloid cells shows a larger monocytic contribution migrating into the young brain, but a larger neutrophilic contribution infiltrating into the aged brain 3 days after stroke. 172 The skull bone marrow houses significant populations of monocytes and neutrophils, with transcriptional signatures distinct from their blood-derived counterparts.…”

Section: Innate Immune Response After Aged Strokementioning

confidence: 94%

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Aging Microbiota-Gut-Brain Axis in Stroke Risk and Outcome

Honarpisheh

Bryan

McCullough

2022

Circulation Research

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The microbiota-gut-brain-axis (MGBA) is a bidirectional communication network between gut microbes and their host. Many environmental and host-related factors affect the gut microbiota. Dysbiosis is defined as compositional and functional alterations of the gut microbiota that contribute to the pathogenesis, progression and treatment responses to disease. Dysbiosis occurs when perturbations of microbiota composition and function exceed the ability of microbiota and its host to restore a symbiotic state. Dysbiosis leads to dysfunctional signaling of the MGBA, which regulates the development and the function of the host’s immune, metabolic, and nervous systems. Dysbiosis-induced dysfunction of the MGBA is seen with aging and stroke, and is linked to the development of common stroke risk factors such as obesity, diabetes, and atherosclerosis. Changes in the gut microbiota are also seen in response to stroke, and may impair recovery after injury. This review will begin with an overview of the tools used to study the MGBA with a discussion on limitations and potential experimental confounders. Relevant MGBA components are introduced and summarized for a better understanding of age-related changes in MGBA signaling and its dysfunction after stroke. We will then focus on the relationship between the MGBA and aging, highlighting that all components of the MGBA undergo age-related alterations that can be influenced by or even driven by the gut microbiota. In the final section, the current clinical and preclinical evidence for the role of MGBA signaling in the development of stroke risk factors such as obesity, diabetes, hypertension, and frailty are summarized, as well as microbiota changes with stroke in experimental and clinical populations. We conclude by describing the current understanding of microbiota-based therapies for stroke including the use of pre-/pro-biotics and supplementations with bacterial metabolites. Ongoing progress in this new frontier of biomedical sciences will lead to an improved understanding of the MGBA’s impact on human health and disease.

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Section: Aging and The Mgbamentioning

confidence: 93%

Section: Aging and The Mgbamentioning

confidence: 93%

Section: Innate Immune Response After Aged Strokementioning

confidence: 94%

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Aging Microbiota-Gut-Brain Axis in Stroke Risk and Outcome

Honarpisheh

Bryan

McCullough

2022

Circulation Research

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“…We are performing previously described methods (15, 16). Briefly, mice were deeply anesthetized by Avertin injection and transcardially perfused with 60mL of sterile, ice-cold phosphate buffered saline (PBS).…”

Section: Methodsmentioning

confidence: 99%

ILC homeostasis phenotyping in various tissues, aging, and sex differences

Mobley

Garrido²,

Honarpisheh³

et al. 2021

Preprint

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Innate lymphoid cells (ILCs) are the innate counterpart to CD4+ T cells that are mediated by the same transcription factors and produce similar cytokines. ILCs are being investigated in many different disease states, but the field current lacks foundational information on ILC representation whether it be in tissues, between males and females, or in aging as these are all vital components in disease etiology and severity. Our descriptive study used flow cytometry to characterize ILCs compared to the entire CD45+ (e.g., lymphocyte) and lineage negative (e.g., ILC) compartments to understand their homeostatic balance and plasticity. Moreover, we defined ILC2 expression and subsets based on their cytokine production and created several mathematical models to elucidate the correlation of extra- and intra-cellular ILC2 markers from least to most complex. ILC studies would benefit from more unbiased, holistic experiments including RNA-seq and mass spectroscopy to further define ILCs in steady-state before adding more complex pathways like different disease states to enhance translational value and therapeutic targeting of these cells.

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“…We have attributed primed microglia as the cell type responsible for this MHCII increase, especially since microglia isolated from aged rats also show increased MHCII gene expression ( Butler et al., 2020 ). However, in addition to resident microglia, a recent study attributes increased antigen presentation in the aged brain to peripherally-sourced APCs, namely DCs and monocyte-derived macrophages ( Honarpisheh et al., 2020 ). Thus, future experiments are needed to further delineate the cell type-specific contribution of antigen presentation in aging and the role of diet and obesity in this process.…”

Section: Brain-resident and Infiltrating Immune Cellsmentioning

confidence: 99%

The role of Western diets and obesity in peripheral immune cell recruitment and inflammation in the central nervous system

Butler

2021

Brain, Behavior, & Immunity - Health

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As the prevalence of obesity and chronic disease increases, the role of nutrition is taking center stage as a potential root cause of not just metabolic-related illnesses, but also of disorders of the central nervous system (CNS). Consumption of a modern, westernized diet, such as a high fat diet (HFD) that contains excess saturated fatty acids (SFAs), refined carbohydrates, and ultra-processed ingredients has been shown to induce neuroinflammation in multiple brain regions important for energy homeostasis, cognitive function, and mood regulation in rodents, non-human primates, and humans. This review article summarizes the literature showing Western diets, via SFA increases, can increase the reactivity and alter the function of multiple types of immune cells from both the innate and adaptive branches of the immune system, with a specific focus on microglia, macrophages, dendritic cells, and T-cells. These changes in immune and neuroimmune signaling have important implications for neuroinflammation and brain health and will be an important factor in future psychoneuroimmunology research.

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Peripherally-sourced myeloid antigen presenting cells increase with advanced aging

Cited by 16 publications

References 86 publications

Aging Microbiota-Gut-Brain Axis in Stroke Risk and Outcome

Aging Microbiota-Gut-Brain Axis in Stroke Risk and Outcome

ILC homeostasis phenotyping in various tissues, aging, and sex differences

The role of Western diets and obesity in peripheral immune cell recruitment and inflammation in the central nervous system

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