GM-CSF and IL-33 Orchestrate Polynucleation and Polyploidy of Resident Murine Alveolar Macrophages in a Murine Model of Allergic Asthma

Quell, Katharina M.; Dutta, Kuheli; Korkmaz, Ülkü R.; Almeida, Larissa Nogueira; Vollbrandt, Tillman; König, Peter; Lewkowich, Ian P.; Deepe, George S.; Verschoor, Admar; Köhl, Jörg; Laumonnier, Yves

doi:10.3390/ijms21207487

Cited by 4 publications

(3 citation statements)

References 66 publications

(90 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In our model system, we observed formation of giant cells from activated macrophages that was sporadic in AAI alone but frequent in AAI preceded by IAV infection. There are little reports on such cells in AAI, but very recently granulocyte-macrophage colony stimulating factor (GM-CSF), IL-13 and IL-33 have been shown to mediate their formation in a house dust mite mediated model of AAI [60]. Their function however is unknown.…”

Section: Discussionmentioning

confidence: 99%

Resolved Influenza A Virus Infection Has Extended Effects on Lung Homeostasis and Attenuates Allergic Airway Inflammation in a Mouse Model

Jorde

Kershaw

et al. 2020

Microorganisms

View full text Add to dashboard Cite

Allergic airway inflammation (AAI) involves T helper cell type 2 (Th2) and pro-inflammatory responses to aeroallergens and many predisposing factors remain elusive. Influenza A virus (IAV) is a major human pathogen that causes acute respiratory infections and induces specific immune responses essential for viral clearance and resolution of the infection. Beyond acute infection, IAV has been shown to persistently affect lung homeostasis and respiratory immunity. Here we asked how resolved IAV infection affects subsequently induced AAI. Mice infected with a sublethal dose of IAV were sensitized and challenged in an ovalbumin mediated mouse model for AAI after resolution of the acute viral infection. Histological changes, respiratory leukocytes, cytokines and airway hyperreactivity were analyzed in resolved IAV infection alone and in AAI with and without previous IAV infection. More than five weeks after infection, we detected persistent pneumonia with increased activated CD4+ and CD8+ lymphocytes as well as dendritic cells and MHCII expressing macrophages in the lung. Resolved IAV infection significantly affected subsequently induced AAI on different levels including morphological changes, respiratory leukocytes and lymphocytes as well as the pro-inflammatory cytokine responses, which was clearly diminished. We conclude that IAV has exceptional persisting effects on respiratory immunity with substantial consequences for subsequently induced AAI.

show abstract

Section: Discussionmentioning

confidence: 99%

Resolved Influenza A Virus Infection Has Extended Effects on Lung Homeostasis and Attenuates Allergic Airway Inflammation in a Mouse Model

Jorde

Kershaw

et al. 2020

Microorganisms

View full text Add to dashboard Cite

show abstract

“…However, the significant dysregulation of cell cycle genes in 2-week-old Nkrp1b − / − mouse AM, as well as the decrease in Ki67 and characteristic hallmarks of S-phase arrest in BrdU staining in Nkrp1b − / − AM, implies a potentially fundamental involvement of NKR-P1B in the renewal of AM 82 , 83 . This is further supported by the appearance of double nuclei in Nkrp1b − / − AM cultured in vitro, which may reflect the consequence of persistent inflammation and DNA damage that is known to result in the formation of polyploid macrophages without cell-to-cell fusion 84 , 85 . Lack of NKR-P1B signaling resulting in the accumulation of toxic lipid species may be the trigger that induces chronic stress on the AM, some of which resort to a polyploid phenotype to preserve genomic stability or it could potentially be caused by a defect in machinery responsible for cytokinesis due to metabolic stress, thus leading to failure of cell division.…”

Section: Discussionmentioning

confidence: 73%

Alveolar macrophage metabolic programming via a C-type lectin receptor protects against lipo-toxicity and cell death

et al. 2022

View full text Add to dashboard Cite

Alveolar macrophages (AM) hold lung homeostasis intact. In addition to the defense against inhaled pathogens and deleterious inflammation, AM also maintain pulmonary surfactant homeostasis, a vital lung function that prevents pulmonary alveolar proteinosis. Signals transmitted between AM and pneumocytes of the pulmonary niche coordinate these specialized functions. However, the mechanisms that guide the metabolic homeostasis of AM remain largely elusive. We show that the NK cell-associated receptor, NKR-P1B, is expressed by AM and is essential for metabolic programming. Nkrp1b−/− mice are vulnerable to pneumococcal infection due to an age-dependent collapse in the number of AM and the formation of lipid-laden AM. The AM of Nkrp1b−/− mice show increased uptake but defective metabolism of surfactant lipids. We identify a physical relay between AM and alveolar type-II pneumocytes that is dependent on pneumocyte Clr-g expression. These findings implicate the NKR-P1B:Clr-g signaling axis in AM-pneumocyte communication as being important for maintaining metabolism in AM.

show abstract

“…HDM‐driven experimental allergic asthma was established by 4× i.t. administration of 100 μg HDM in 50 μL PBS on days 0, 7, 14, and 21 17,72 . Mice were sacrificed and organs were harvested 72 h after the final immunization for further analysis (Figure S1A).…”

Section: Methodsmentioning

confidence: 99%

C5aR1 activation in mice controls inflammatory eosinophil recruitment and functions in allergic asthma

Wiese

Duhn

Korkmaz

et al. 2023

Allergy

Self Cite

View full text Add to dashboard Cite

Background Pulmonary eosinophils comprise at least two distinct populations of resident eosinophils (rEOS) and inflammatory eosinophils (iEOS), the latter recruited in response to pulmonary inflammation. Here, we determined the impact of complement activation on rEOS and iEOS trafficking and function in two models of pulmonary inflammation. Methods BALB/c wild‐type and C5ar1−/− mice were exposed to different allergens or IL‐33. Eosinophil populations in the airways, lung, or mediastinal lymph nodes (mLN) were characterized by FACS or immunohistochemistry. rEOS and iEOS functions were determined in vivo and in vitro. Results HDM and IL‐33 exposure induced a strong accumulation of iEOS but not rEOS in the airways, lungs, and mLNs. rEOS and iEOS expressed C3/C5 and C5aR1, which were significantly higher in iEOS. Initial pulmonary trafficking of iEOS was markedly reduced in C5ar1−/− mice and associated with less IL‐5 production from ILC2 cells. Functionally, adoptively transferred pulmonary iEOS from WT but not from C5ar1−/− mice‐induced airway hyperresponsiveness (AHR), which was associated with significantly reduced C5ar1−/− iEOS degranulation. Pulmonary iEOS but not rEOS were frequently associated with T cells in lung tissue. After HDM or IL‐33 exposure, iEOS but not rEOS were found in mLNs, which were significantly reduced in C5ar1−/− mice. C5ar1−/− iEOS expressed less costimulatory molecules, associated with a decreased potency to drive antigen‐specific T cell proliferation and differentiation into memory T cells. Conclusions We uncovered novel roles for C5aR1 in iEOS trafficking and activation, which affects key aspects of allergic inflammation such as AHR, ILC2, and T cell activation.

show abstract

GM-CSF and IL-33 Orchestrate Polynucleation and Polyploidy of Resident Murine Alveolar Macrophages in a Murine Model of Allergic Asthma

Cited by 4 publications

References 66 publications

Resolved Influenza A Virus Infection Has Extended Effects on Lung Homeostasis and Attenuates Allergic Airway Inflammation in a Mouse Model

Resolved Influenza A Virus Infection Has Extended Effects on Lung Homeostasis and Attenuates Allergic Airway Inflammation in a Mouse Model

Alveolar macrophage metabolic programming via a C-type lectin receptor protects against lipo-toxicity and cell death

C5aR1 activation in mice controls inflammatory eosinophil recruitment and functions in allergic asthma

Contact Info

Product

Resources

About