Macrophage and dendritic cell subset composition can distinguish endotypes in adjuvant-induced asthma mouse models

Özkan, Mustafa; Eskiocak, Yusuf Cem; Wingender, Gerhard

doi:10.1371/journal.pone.0250533

Cited by 6 publications

(4 citation statements)

References 86 publications

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“…This finding is consistent with the results reported by R S Peebles Jr et al. ( 22 ).Th2-type cytokines were prevalent in eosinophilic asthma, whereas Th1-type and Th17-type cytokines have been implicated in neutrophilic asthma ( 23 ). In PVM-OVA group, Th1/Th17 type cytokines increased.…”

Section: Resultssupporting

confidence: 92%

Proline metabolism reprogramming of trained macrophages induced by early respiratory infection combined with allergen sensitization contributes to development of allergic asthma in childhood of mice

et al. 2022

Front. Immunol.

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BackgroundInfants with respiratory syncytial virus (RSV)-associated bronchiolitis are at increased risk of childhood asthma. Recent studies demonstrated that certain infections induce innate immune memory (also termed trained immunity), especially in macrophages, to respond more strongly to future stimuli with broad specificity, involving in human inflammatory diseases. Metabolic reprogramming increases the capacity of the innate immune cells to respond to a secondary stimulation, is a crucial step for the induction of trained immunity. We hypothesize that specific metabolic reprogramming of lung trained macrophages induced by neonatal respiratory infection is crucial for childhood allergic asthma.ObjectiveTo address the role of metabolic reprogramming in lung trained macrophages induced by respiratory virus infection in allergic asthma.MethodsNeonatal mice were infected and sensitized by the natural rodent pathogen Pneumonia virus of mice (PVM), a mouse equivalent strain of human RSV, combined with ovalbumin (OVA). Lung CD11b+ macrophages in the memory phase were re-stimulated to investigate trained immunity and metabonomics. Adoptive transfer, metabolic inhibitor and restore experiments were used to explore the role of specific metabolic reprogramming in childhood allergic asthma.ResultsPVM infection combined with OVA sensitization in neonatal mice resulted in non-Th2 (Th1/Th17) type allergic asthma following OVA challenge in childhood of mice. Lung CD11b+ macrophages in the memory phage increased, and showed enhanced inflammatory responses following re-stimulation, suggesting trained macrophages. Adoptive transfer of the trained macrophages mediated the allergic asthma in childhood. The trained macrophages showed metabolic reprogramming after re-stimulation. Notably, proline biosynthesis remarkably increased. Inhibition of proline biosynthesis suppressed the development of the trained macrophages as well as the Th1/Th17 type allergic asthma, while supplement of proline recovered the trained macrophages as well as the allergic asthma.ConclusionProline metabolism reprogramming of trained macrophages induced by early respiratory infection combined with allergen sensitization contributes to development of allergic asthma in childhood. Proline metabolism could be a well target for prevention of allergic asthma in childhood.

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Section: Resultssupporting

confidence: 92%

Proline metabolism reprogramming of trained macrophages induced by early respiratory infection combined with allergen sensitization contributes to development of allergic asthma in childhood of mice

et al. 2022

Front. Immunol.

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“…Therefore, each equation symbol is defined below: n: sample size; Sa and Sb: standard deviation of the variable in each group; Z α/2 : value of error α, chosen as 1.96 (5%); Z β : value of error β, chosen as 0.84 (20%); d: minimum difference between the mean values. Taking into consideration published data in an asthma model, for IgE levels, Lactobacilli amounts, and Eosinophil infiltrates, we considered Eosinophil infiltrates from previous published data (ÖZKAN et al, 2021), since this was the variable with the largest number of mice needed. Then, according to the data presented in the paper above cited, we assumed Sa = 1, Sb = 2,5, d = 5 [values from eosinophil percentages inside lung samples from mice immunized with Complete Freund's Adjuvant (CFA) + Ovalbumin (OVA)] and the result was 3.76.…”

Section: Animalsmentioning

confidence: 99%

A story with two versions: yacon root pulp on experimental asthma in different animal facilities

Mendes,

Caetano,

Arpini

et al. 2024

Cienc. Rural

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The intestinal microbiota has an important role in animal health. Therefore, prebiotics have gained interest in the scientific community for their role in manipulating populations of intestinal microorganisms. Among prebiotics, there is Smallanthus sonchifolius Poepp. Endl (yacon) root, which can be ingested in natura or in different forms, such as flours and extracts. This prebiotic has been associated with beneficial effects in different diseases, including metabolic (like type 2 diabetes) and immunological disorders. Thus, mouse models of human diseases caused by immunological factors have been used to better understand the prebiotic effects of yacon. Since prebiotics interfere with animal microbiota, it is important to take into consideration the quality level of mouse facilities. In this way, the beneficial effects of a yacon root pulp were tested in a mouse model of allergic asthma and, considering how animal facility conditions could affect those results, we performed experiments both in conventional facilities and specific pathogen-free (SPF) ones. Our results showed that better prebiotic effects were observed in a SPF facility than in a conventional one and, in some cases, evidence of yacon beneficial effects was observed exclusively in a SPF facility. For example, there were reductions of 63.6% and 58.0% in IgE and eosinophils, respectively, in immunized/yacon-treated animals compared to immunized mice only. Taken together, our results not only showed the beneficial effects of yacon root pulp in an asthma model but also demonstrated the relevance of performing experiments with prebiotics in SPF facilities.

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“…[141] Others have shown in models of neutrophilic asthma (more severe and refractory to steroid treatments) that pDCs are the primary DC subset involved as they are markedly increased in BAL fluid of mice with neutrophilic asthma in contrast to the eosinophilic asthma. [142] Furthermore, neutrophils have been shown to activate pDCs in both humans and mouse models. [143,144] Taken together, these data indicate that the role of pDCs in disease may depend on the underlying pathophysiology of the disease (neutrophilic > eosinophilic asthma and chronic>acute) as well as potential functional differences among subsets.…”

Section: Mouse Pdcsmentioning

confidence: 99%

Catching Our Breath: Updates on the Role of Dendritic Cell Subsets in Asthma

Lajiness

Cook‐Mills

2023

Advanced Biology

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Dendritic cells (DCs), as potent antigen presenting cells, are known to play a central role in the pathophysiology of asthma. The understanding of DC biology has evolved over the years to include multiple subsets of DCs with distinct functions in the initiation and maintenance of asthma. Furthermore, asthma is increasingly recognized as a heterogeneous disease with potentially diverse underlying mechanisms. The goal of this review is to summarize the role of DCs and the various subsets therein in the pathophysiology of asthma and highlight some of the crucial animal models shaping the field today. Potential future avenues of investigation to address existing gaps in knowledge are discussed.

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Macrophage and dendritic cell subset composition can distinguish endotypes in adjuvant-induced asthma mouse models

Cited by 6 publications

References 86 publications

Proline metabolism reprogramming of trained macrophages induced by early respiratory infection combined with allergen sensitization contributes to development of allergic asthma in childhood of mice

Proline metabolism reprogramming of trained macrophages induced by early respiratory infection combined with allergen sensitization contributes to development of allergic asthma in childhood of mice

A story with two versions: yacon root pulp on experimental asthma in different animal facilities

Catching Our Breath: Updates on the Role of Dendritic Cell Subsets in Asthma

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