GM-CSF Priming Drives Bone Marrow-Derived Macrophages to a Pro-Inflammatory Pattern and Downmodulates PGE2 in Response to TLR2 Ligands

Sorgi, Carlos Artério; Rose, Stéphanie; Court, Nathalie; Carlos, Daniela; Paula-Silva, Francisco Wanderley Garcia; Assis, Patrícia A.; Frantz, Fabiani Gai; Ryffel, Bernhard; Quesniaux, Valérie; Faccioli, Lúcia Helena

doi:10.1371/journal.pone.0040523

Cited by 33 publications

(32 citation statements)

References 65 publications

(69 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this study, we showed that high potential of SKG T cells to produce GM-CSF produced a different outcome between zymosan-treated SKG and BALB/c. GM-CSF was reported to upregulate TLR2, TLR4, and CD14 expression (41)(42)(43) and boost IL-6 and IL-1b production from macrophages (41,44,45). Although serum concentration of GM-CSF in zymosan-treated SKG mice was very low and could not be detected by ELISA, we showed that GM-CSF could enhance the production of IL-6 and IL-1b by macrophages even at a low concentration (Fig.…”

Section: Discussionmentioning

confidence: 73%

GM-CSF but Not IL-17 Is Critical for the Development of Severe Interstitial Lung Disease in SKG Mice

Shiomi

Usui

Ishikawa

et al. 2014

The Journal of Immunology

View full text Add to dashboard Cite

Interstitial lung disease (ILD) is a common complication and sometimes a prognostic factor of connective tissue diseases (CTDs) in humans. However, suitable animal model of severe CTD-associated ILD (CTD-ILD) has been limited. In this study, we showed that zymosan-treated SKG mice developed not only arthritis but also chronic–progressive ILD with high mortality over several months. The pathological and clinical features of ILD in zymosan-treated SKG mice were similar to that of human severe CTD-ILD. ILD in this mouse was characterized by massive infiltration of Th17 cells, GM-CSF–producing CD4+ T cells, and CD11b+ Gr1+ neutrophils with fibrosis. Naive SKG T cells were skewed to differentiate into GM-CSF–producing cells, and GM-CSF secreted by T cells enhanced IL-6 and IL-1β production by macrophages, which in turn enhanced differentiation of IL-17A– and/or GM-CSF–producing T cells and infiltration of neutrophils into lung. Neutralization of GM-CSF completely blocked the development of this ILD, and the blocking of IL-6 signaling resulted in partial prevention of it, whereas neutralization of IL-17A did not. In contrast, the progression of arthritis was inhibited by the neutralization of GM-CSF and slightly by the neutralization of IL-17A, but not by the blocking of IL-6 signaling. These data suggested zymosan-treated SKG mice could be a useful mouse model of severe CTD-ILD, and GM-CSF, rather than IL-17A or IL-6, contributed to the development of ILD in zymosan-treated SKG mice, indicating that neutralization of GM-CSF would be a useful therapeutic strategy for severe CTD-ILD.

show abstract

Section: Discussionmentioning

confidence: 73%

GM-CSF but Not IL-17 Is Critical for the Development of Severe Interstitial Lung Disease in SKG Mice

Shiomi

Usui

Ishikawa

et al. 2014

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…(3) Additionally, iM and iDC in the naïve situation have differentiated under influence of M-CSF, which makes them more responsive to T1-IFN signaling (94). During progression of Mtb infection, GM-CSF levels rise and increase the potential for IL-1β production by iM and iDC (94, 125, 155, 156). (4) Similar to the situation in gut infection, we propose that in tuberculosis (TB) IL-12 production in the lungs stimulates IFN-γ production by bone-marrow-resident NK cells, which locally primes monocytes (154).…”

Section: T1-ifns In Tbmentioning

confidence: 99%

“…(5) Additionally, IFN-γ stimulates monopoiesis over granulopoiesis by granulocyte/macrophage progenitor cells (128). (6) As Mtb infection progresses and GM-CSF levels increase, iM and iDC readily produce IL-1β [see also (3)] (124, 155), which can lead to PMN-mediated inflammatory damage in TB (120). (7) IL-1β production can be inhibited in response to either IFN-γ or IFN-β through mechanistically distinct pathways that differently affect Mtb killing.…”

Section: T1-ifns In Tbmentioning

confidence: 99%

Interactions between Type 1 Interferons and the Th17 Response in Tuberculosis: Lessons Learned from Autoimmune Diseases

et al. 2017

View full text Add to dashboard Cite

The classical paradigm of tuberculosis (TB) immunity, with a central protective role for Th1 responses and IFN-γ-stimulated cellular responses, has been challenged by unsatisfactory results of vaccine strategies aimed at enhancing Th1 immunity. Moreover, preclinical TB models have shown that increasing IFN-γ responses in the lungs is more damaging to the host than to the pathogen. Type 1 interferon signaling and altered Th17 responses have also been associated with active TB, but their functional roles in TB pathogenesis remain to be established. These two host responses have been studied in more detail in autoimmune diseases (AID) and show functional interactions that are of potential interest in TB immunity. In this review, we first identify the role of type 1 interferons and Th17 immunity in TB, followed by an overview of interactions between these responses observed in systemic AID. We discuss (i) the effects of GM-CSF-secreting Th17.1 cells and type 1 interferons on CCR2+ monocytes; (ii) convergence of IL-17 and type 1 interferon signaling on stimulating B-cell activating factor production and the central role of neutrophils in this process; and (iii) synergy between IL-17 and type 1 interferons in the generation and function of tertiary lymphoid structures and the associated follicular helper T-cell responses. Evaluation of these autoimmune-related pathways in TB pathogenesis provides a new perspective on recent developments in TB research.

show abstract

“…In general it functions as a white blood cell growth factor. In addition, it has been shown to have roles in cell signaling [38] and in promoting inflammatory dendritic cells [39] and macrophages [40]. Furthermore, it has been implicated in the pathology of lung injury [41] and arthritic pain [42].…”

Section: Discussionmentioning

confidence: 99%

The Inflammatory Cytokine IL-21 is Expressed by Splenic Neutrophils in Response to Transplantation of Allogeneic Cells

Thompson

Hardin

Glass

et al. 2016

SOJI

View full text Add to dashboard Cite

We have previously reported that GR-1 neutrophil/monocytes rose dramatically in the spleen, peaked by day 7 and declined through day 14. This period corresponded to the peak of acute Graft-Versus-Host Disease (aGVHD) in BALB/c mice transplanted with allogeneic donor cells. We now asked: what cytokines did these splenic neutrophil/monocytes express on day 7 and 14 post transplant? BALB/c mice were transplanted with allogeneic B6 or syngeneic BALB/c donor cells. Long term survival was recorded through day 31. Other groups were sacrificed on days 3, 5, 7, 14, 21 and 31 days post transplant to record the total number of cells in the spleens and their phenotypes. Neutrophils were isolated from the spleens of mice transplanted with B6 and BALB/c cells on days 7 and 14.Daily body weight demonstrated a transient drop in the syngeneic transplants on day 2 but a much greater drop with its nadir at day 7 and never fully recovering through 31 days. CD8/CD4 T lymphocytes peaked in the spleen on day 5 and were followed on day 7 by GR-I cells in all of the allogeneic transplants. In syngeneic transplants this early rise in lymphocytes did not occur and GR-1 cells peaked on day 14. Highly purified neutrophils were isolated in two separate experiments from the spleens on days 7 and 14 post transplant. In both experiments day 7 allogeneic neutrophils expressed significantly elevated levels of Interleukin-21 (IL-21) mRNA whereas the day 7 and 14 syngeneic cells expressed lower but significant levels of TNFα. Intracellular IL-21 was demonstrated in the allogeneic neutrophils on day 7 before and after in vitro stimulation.In conclusion Purified neutrophils isolated from the spleen on day 7, the early peak of allogeneic transplantation a GVHD, express high levels of IL-21 message and intracellular IL-21.

show abstract

GM-CSF Priming Drives Bone Marrow-Derived Macrophages to a Pro-Inflammatory Pattern and Downmodulates PGE2 in Response to TLR2 Ligands

Cited by 33 publications

References 65 publications

GM-CSF but Not IL-17 Is Critical for the Development of Severe Interstitial Lung Disease in SKG Mice

GM-CSF but Not IL-17 Is Critical for the Development of Severe Interstitial Lung Disease in SKG Mice

Interactions between Type 1 Interferons and the Th17 Response in Tuberculosis: Lessons Learned from Autoimmune Diseases

The Inflammatory Cytokine IL-21 is Expressed by Splenic Neutrophils in Response to Transplantation of Allogeneic Cells

Contact Info

Product

Resources

About