Unprimed, M1 and M2 Macrophages Differentially Interact with Porphyromonas gingivalis

Lam, Roselind S.; O'Brien-Simpson, Neil M; Holden, Joseph; Lenzo, Jason C.; Fong, Shao Bing; Reynolds, Eric C.

doi:10.1371/journal.pone.0158629

Cited by 71 publications

(70 citation statements)

References 56 publications

(58 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Our data indicate that S. mansoni infection induces a hybrid inflammatory state in male but not female BMDM, where the LPS induced production of nitrite and iNOS is enhanced, while the production of the key chronic pro-inflammatory mediators IL-12p70, CXCL1, and IL-6 are reduced. This inflammatory profile is distinct from what has previously been published with IL-4 induced M2 macrophages, where the production of iNOS and nitrite are reduced following TLR stimulation [67]. CXCL1 and IL-6 have previously been linked to increased monocyte recruitment and disease progression in both atherosclerosis and obesity-induced diabetes [68-72], so these data support the possibility of infection driven modulation of macrophage function supporting the decreased pathology seen in infected males.…”

Section: Discussionsupporting

confidence: 51%

Schistosoma mansoniinfection reprograms the metabolic potential of the myeloid lineage in a mouse model of metabolic syndrome

Cortés-Selva

Gibbs

Maschek

et al. 2020

Preprint

View full text Add to dashboard Cite

44 45 Despite strong evidence that helminth infections are protective against the development of 46 metabolic disease, a major gap exists in understanding the mechanism(s) underlying this. We 47 have previously found that Schistosoma mansoni induces profound alterations to the metabolic 48 transcriptome of hepatic macrophages and protects male ApoE -/on high fat diet from the 49 development of obesity, glucose intolerance, and atherosclerosis. Here we demonstrate that 50 macrophages derived from the bone marrow (BMDM) of S. mansoni infected male ApoE -/mice 51 have dramatically increased mitochondrial respiration and mitochondrial mass compared to those 52 from uninfected mice. This change is accompanied by increased glucose and palmitate shuttling 53 into TCA cycle intermediates and decreased accumulation of cellular cholesterol esters. The 54 systemic effects of metabolic modulation by schistosome infection are a function of biological 55 sex, where schistosome infection protects ApoE -/male mice from obesity, glucose intolerance, 56 and increased serum triglycerides, but not female mice. The sex-dependent effects of infection 57 extend to myeloid cells specifically, where metabolic reprogramming leads to opposite 58 cholesterol phenotypes in BMDM from infected females and males. Finally, we demonstrate that 59 the metabolic reprogramming of male myeloid cells is transferrable via bone marrow 60 transplantation to an uninfected host, indicating maintenance of reprogramming in the absence of 61 ongoing schistosome antigen exposure. This work provides strong evidence that S. 62 mansoni systemically reprograms the metabolism of the myeloid compartment in a sex-63 dependent manner. 64 65 Author Summary 66Globally helminth endemic regions have lower incidences of metabolic disease. Schistosomiasis 67 in particular has been shown to protect male mice from the development of atherosclerosis, 68 diabetes and obesity while altering the metabolism of liver macrophages. In this present study we 69 sought to understand if metabolic modulation occurs systemically, and if these effects occur in 70 females as well. We have found for the first time that macrophages generated from bone marrow 71 myeloid progenitors from infected male mice have long-lived increases in their basal metabolism 72 of lipids. We have also found that unlike male mice, female mice infected with Schistosoma 73 mansoni are not protected from the development of diabetes and obesity. S. mansoni infection 74 induces opposite changes to macrophage transcription and metabolism in males and females. 75Importantly we demonstrate that the changes to male macrophage metabolism can be transferred 76to an uninfected host. This suggests that metabolic reprogramming is long-lived without 77 exposure to active infection, and the development of a memory-like phenotype. 78 79 80 Introduction 81 82 Cardiovascular disease (CVD) is the leading worldwide cause of mortality [1, 2]. In the United 83States, 65% of adults diagnosed with diabetes have elevated LDL cholestero...

show abstract

Section: Discussionsupporting

confidence: 51%

Schistosoma mansoniinfection reprograms the metabolic potential of the myeloid lineage in a mouse model of metabolic syndrome

Cortés-Selva

Gibbs

Maschek

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…Since chemerin is chemoattractant for immune cells that are implicated in the pathogenesis of periodontal disease, including DCs, macrophages, and NK cells (37–41), we next tested whether chemerin in GCF samples from individuals with gingivitis and periodontitis is able to support chemotaxis of chemerin responsive CMKLR1 + cells. We performed in vitro transwell chemotaxis assays using the GCF samples each containing 1 nM endogenous chemerin (as determined by ELISA) and 1 nM bioactive chemS157 as a positive control.…”

Section: Resultsmentioning

confidence: 99%

“…Chemerin-mediated chemotaxis, exhibited by the gingivitis samples (Figure 6A), may serve to enhance the recruitment of CMKLR1 + cells to inflamed gums. CMKLR1+ DCs, macrophages, and NK cells have been associated with inflammatory gum disease and reported to infiltrate the inflamed gingiva (37–41). Although their role in gingivitis or periodontitis is not well defined, they are considered to be a part of the defense mechanism against microbial challenge in dental biofilm (37–41).…”

Section: Discussionmentioning

confidence: 99%

“…CMKLR1+ DCs, macrophages, and NK cells have been associated with inflammatory gum disease and reported to infiltrate the inflamed gingiva (37–41). Although their role in gingivitis or periodontitis is not well defined, they are considered to be a part of the defense mechanism against microbial challenge in dental biofilm (37–41). However, since the innate immune response to microbes can lead to excessive inflammation and its associated damaging effects on healthy host tissue, these cells may also contribute to the pathogenesis of periodontal disease (37–41).…”

Section: Discussionmentioning

confidence: 99%

“…Although their role in gingivitis or periodontitis is not well defined, they are considered to be a part of the defense mechanism against microbial challenge in dental biofilm (37–41). However, since the innate immune response to microbes can lead to excessive inflammation and its associated damaging effects on healthy host tissue, these cells may also contribute to the pathogenesis of periodontal disease (37–41). In contrast to gingivitis, periodontitis is associated with a marked reduction in chemerin bioactivity (Figure 6A).…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Antimicrobial and Attractant Roles for Chemerin in the Oral Cavity during Inflammatory Gum Disease

et al. 2017

View full text Add to dashboard Cite

Periodontal inflammation is one of the most common chronic inflammatory conditions in humans. Despite recent advances in identifying and characterizing oral microbiota dysbiosis in the pathogenesis of gum disease, just how host factors maintain a healthy homeostatic oral microbial community or prevent the development of a pathogenic oral microbiota remains poorly understood. An important determinant of microbiota fate is local antimicrobial proteins. Here, we report that chemoattractant protein chemerin, which we recently identified as a potent endogenous antimicrobial agent in body barriers such as the skin, is present in the oral cavity under homeostatic and inflammatory conditions. Chemerin and a chemerin-derived antimicrobial peptide are bactericidal against select bacteria strategically positioned in dental biofilm. Gingival crevicular samples from patients with gingivitis but not periodontitis contain abundant bioactive chemerin capable of inducing CMKLR1-dependent leukocyte migration. Gingipains secreted by the periodontopathogen P. gingivalis inactivate chemerin. Together, these data suggest that as an antimicrobial agent and leukocyte chemoattractant, chemerin likely contributes to antimicrobial immune defense in the oral cavity.

show abstract

Neonatal Osteomacs and Bone Marrow Macrophages Differ in Phenotypic Marker Expression and Function

Mohamad

Gunawan

Blosser

et al. 2020

Journal of Bone and Mineral Research

View full text Add to dashboard Cite

Osteomacs (OM) are specialized bone‐resident macrophages that are a component of the hematopoietic niche and support bone formation. Also located in the niche are a second subset of macrophages, namely bone marrow–derived macrophages (BM Mφ). We previously reported that a subpopulation of OM co‐express both CD166 and CSF1R, the receptor for macrophage colony‐stimulating factor (MCSF), and that OM form more bone‐resorbing osteoclasts than BM Mφ. Reported here are single‐cell quantitative RT‐PCR (qRT‐PCR), mass cytometry (CyTOF), and marker‐specific functional studies that further identify differences between OM and BM Mφ from neonatal C57Bl/6 mice. Although OM express higher levels of CSF1R and MCSF, they do not respond to MCSF‐induced proliferation, in contrast to BM Mφ. Moreover, receptor activator of NF‐κB ligand (RANKL), without the addition of MCSF, was sufficient to induce osteoclast formation in OM but not BM Mφ cultures. OM express higher levels of CD166 than BM Mφ, and we found that osteoclast formation by CD166−/− OM was reduced compared with wild‐type (WT) OM, whereas CD166−/− BM Mφ showed enhanced osteoclast formation. CD110/c‐Mpl, the receptor for thrombopoietin (TPO), was also higher in OM, but TPO did not alter OM‐derived osteoclast formation, whereas TPO stimulated BM Mφ osteoclast formation. CyTOF analyses demonstrated OM uniquely co‐express CD86 and CD206, markers of M1 and M2 polarized macrophages, respectively. OM performed equivalent phagocytosis in response to LPS or IL‐4/IL‐10, which induce polarization to M1 and M2 subtypes, respectively, whereas BM Mφ were less competent at phagocytosis when polarized to the M2 subtype. Moreover, in contrast to BM Mφ, LPS treatment of OM led to the upregulation of CD80, an M1 marker, as well as IL‐10 and IL‐6, known anti‐inflammatory cytokines. Overall, these data reveal that OM and BM Mφ are distinct subgroups of macrophages, whose phenotypic and functional differences in proliferation, phagocytosis, and osteoclast formation may contribute physiological specificity during health and disease. © 2021 American Society for Bone and Mineral Research (ASBMR).

show abstract

Unprimed, M1 and M2 Macrophages Differentially Interact with Porphyromonas gingivalis

Cited by 71 publications

References 56 publications

Schistosoma mansoniinfection reprograms the metabolic potential of the myeloid lineage in a mouse model of metabolic syndrome

Schistosoma mansoniinfection reprograms the metabolic potential of the myeloid lineage in a mouse model of metabolic syndrome

Antimicrobial and Attractant Roles for Chemerin in the Oral Cavity during Inflammatory Gum Disease

Neonatal Osteomacs and Bone Marrow Macrophages Differ in Phenotypic Marker Expression and Function

Contact Info

Product

Resources

About