CD14 is critical for TLR2-mediated M1 macrophage activation triggered by N-glycan recognition

Silva, Thiago Aparecido da; Zorzetto-Fernandes, Andre Luiz; Cecílio, Nerry T.; Sardinha-Silva, Aline; Fernandes, Fabrício Freitas; Roque-Barreira, Maria Cristina

doi:10.1038/s41598-017-07397-0

Cited by 65 publications

(56 citation statements)

References 77 publications

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“…Among the shared target genes, Cd14 is a glycosylphosphatidylinositol-anchored receptor known as a co-receptor for TLRs [65] and critical for Tlr2mediated macrophage activation [66]. Absence of Cd14 delays progression of prion diseases accompanied by increased microglial activation [67].…”

Section: Discussionmentioning

confidence: 99%

Core transcriptional regulatory circuits in prion diseases

et al. 2020

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Complex diseases involve dynamic perturbations of pathophysiological processes during disease progression. Transcriptional programs underlying such perturbations are unknown in many diseases. Here, we present core transcriptional regulatory circuits underlying early and late perturbations in prion disease. We first identified cellular processes perturbed early and late using time-course gene expression data from three prion-infected mouse strains. We then built a transcriptional regulatory network (TRN) describing regulation of early and late processes. We found over-represented feed-forward loops (FFLs) comprising transcription factor (TF) pairs and target genes in the TRN. Using gene expression data of brain cell types, we further selected active FFLs where TF pairs and target genes were expressed in the same cell type and showed correlated temporal expression changes in the brain. We finally determined core transcriptional regulatory circuits by combining these active FFLs. These circuits provide insights into transcriptional programs for early and late pathophysiological processes in prion disease.

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Section: Discussionmentioning

confidence: 99%

Core transcriptional regulatory circuits in prion diseases

et al. 2020

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“…115,116 In the innate immune response, when macrophages exposed to certain stimuli, such as LPS-peptide complexes, are recognized by TLRs and CD14, signaling cascades might be initiated that generate reactive oxygen and nitrogen species and inflammatory cytokines such as IFNα and IFN-β. [117][118][119] During the humoral response, phagocytosis of certain microorganisms might be mediated by recognition of the Fc portion. 120 Specific costimulatory molecules act as a key step in enhancing phagocytosis, antigen presentation, and endocytosis.…”

Section: Markers Of M1 M2 and M4 Macrophagesmentioning

confidence: 99%

<p>Functional aspects, phenotypic heterogeneity, and tissue immune response of macrophages in infectious diseases</p>

Sousa¹,

Vasconcelos²,

Quaresma³

2019

IDR

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Macrophages are a functionally heterogeneous group of cells with specialized functions depending not only on their subgroup but also on the function of the organ or tissue in which the cells are located. The concept of macrophage phenotypic heterogeneity has been investigated since the 1980s, and more recent studies have identified a diverse spectrum of phenotypic subpopulations. Several types of macrophages play a central role in the response to infectious agents and, along with other components of the immune system, determine the clinical outcome of major infectious diseases. Here, we review the functions of various macrophage phenotypic subpopulations, the concept of macrophage polarization, and the influence of these cells on the evolution of infections. In addition, we emphasize their role in the immune response in vivo and in situ, as well as the molecular effectors and signaling mechanisms used by these cells. Furthermore, we highlight the mechanisms of immune evasion triggered by infectious agents to counter the actions of macrophages and their consequences. Our aim here is to provide an overview of the role of macrophages in the pathogenesis of critical transmissible diseases and discuss how elucidation of this relationship could enhance our understanding of the host–pathogen association in organ-specific immune responses.

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“…The co‐receptor CD14 is crucial in Borrelia recognition in collaboration with TLR2 . Interestingly, a study by Sahay et al suggests that CD14 may be important in Borrelia clearance and tolerization of macrophages, through SOCS1 and SOCS3 signaling, whose pathways have also been linked to MMP production and degradation of collagen .…”

Section: The Role Of the Innate Immune System During The Early Stagesmentioning

confidence: 99%

“…168 The co-receptor CD14 is crucial in Borrelia recognition in collaboration with TLR2. [173][174][175][176] Interestingly, a study by Sahay et al 177 suggests that CD14 may be important in Borrelia clearance and tolerization of macrophages, through SOCS1 and SOCS3 signaling, whose pathways have also been linked to MMP production and degradation of collagen. 178,179 CD14 deficiency in mice reduced these effects significantly and led to higher bacterial burdens and more severe and persistent inflammation.…”

Section: Inhibition Of Myostatin In Vivo Suppressed Lyme Arthritis Inmentioning

confidence: 99%

A joint effort: The interplay between the innate and the adaptive immune system in Lyme arthritis

Brouwer

Schoor

Vrijmoeth

et al. 2020

Immunological Reviews

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Articular joints are a major target of Borrelia burgdorferi, the causative agent of Lyme arthritis. Despite antibiotic treatment, recurrent or persistent Lyme arthritis is observed in a significant number of patients. The host immune response plays a crucial role in this chronic arthritic joint complication of Borrelia infections. During the early stages of B. burgdorferi infection, a major hinder in generating a proper host immune response is the lack of induction of a strong adaptive immune response. This may lead to a delayed hyperinflammatory reaction later in the disease. Several mechanisms have been suggested that might be pivotal for the development of Lyme arthritis and will be highlighted in this review, from molecular mimicry of matrix metallopeptidases and glycosaminoglycans, to autoimmune responses to live bacteria, or remnants of Borrelia spirochetes in joints. Murine studies have suggested that the inflammatory responses are initiated by innate immune cells, but this does not exclude the involvement of the adaptive immune system in this dysregulated immune profile. Genetic predisposition, via human leukocyte antigen‐DR isotype and microRNA expression, has been associated with the development of antibiotic‐refractory Lyme arthritis. Yet the ultimate cause for (antibiotic‐refractory) Lyme arthritis remains unknown. Complex processes of different immune cells and signaling cascades are involved in the development of Lyme arthritis. When these various mechanisms are fully been unraveled, new treatment strategies can be developed to target (antibiotic‐refractory) Lyme arthritis more effectively.

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CD14 is critical for TLR2-mediated M1 macrophage activation triggered by N-glycan recognition

Cited by 65 publications

References 77 publications

Core transcriptional regulatory circuits in prion diseases

Core transcriptional regulatory circuits in prion diseases

<p>Functional aspects, phenotypic heterogeneity, and tissue immune response of macrophages in infectious diseases</p>

A joint effort: The interplay between the innate and the adaptive immune system in Lyme arthritis

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