TCRβ Combinatorial Immunoreceptor Expression by Neutrophils Correlates with Parasite Burden and Enhanced Phagocytosis during a Plasmodium berghei ANKA Malaria Infection

Chorazeczewski, Joanna K.; Aleshnick, Maya; Majam, Victoria; Okoth, Winter A.; Kurapova, Regina; Akue, Adovi; KuKuruga, Mark; Kumar, Sanjai; Oakley, Miranda S.

doi:10.1128/iai.00899-17

Cited by 12 publications

(6 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, recent studies provide conclusive evidence that small subpopulations of monocytes, the second major phagocyte population in the circulation next to neutrophils, also constitutively express TCRαβ variable immune receptors [8] , [9] . Importantly, both the TCRαβ in neutrophils and in macrophages have been implicated by us and others in disease [10] , [11] , [12] , [13] , [14] . Of note, most recent studies from our laboratory and others provide evidence for the expression of the second variable immune receptor based on immunoglobulin heavy and light chain genes by cells of the myeloid lineage [15] , [16] , [17] .…”

Section: Introductionmentioning

confidence: 83%

Trilineage Sequencing Reveals Complex TCRβ Transcriptomes in Neutrophils and Monocytes Alongside T Cells

Fuchs

Püellmann²,

Wang

et al. 2021

Genomics, Proteomics &Amp; Bioinformatics

View full text Add to dashboard Cite

Recent findings indicate the presence of T cell receptor (TCR)-based combinatorial immune receptors beyond T cells in neutrophils and monocytes/macrophages. In this study, using a semiquantitative trilineage immune repertoire sequencing approach as well as under rigorous bioinformatic conditions, we identify highly complex TCRβ transcriptomes in human circulating monocytes and neutrophils that separately encode repertoire diversities one and two orders of magnitude smaller than that of T cells. Intraindividual transcriptomic analyses reveal that neutrophils, monocytes, and T cells express distinct TCRβ repertoires with less than 0.1% overall trilineage repertoire sharing. Interindividual comparison shows that in all three leukocyte lineages, the vast majority of the expressed TCRβ variants are private. We also find that differentiation of monocytes into macrophages induces dramatic individual-specific repertoire shifts, revealing a surprising degree of immune repertoire plasticity in the monocyte lineage. These results uncover the remarkable complexity of the two phagocyte-based flexible immune systems which until now has been hidden in the shadow of T cells.

show abstract

Section: Introductionmentioning

confidence: 83%

Trilineage Sequencing Reveals Complex TCRβ Transcriptomes in Neutrophils and Monocytes Alongside T Cells

Fuchs

Püellmann²,

Wang

et al. 2021

Genomics, Proteomics &Amp; Bioinformatics

View full text Add to dashboard Cite

show abstract

“…Ensuing studies showed the recombination of TCR αβ/γδ in monocytes and macrophages [9, 10] as well as TCR γδ in eosinophils [11]. Interestingly, recent studies present the induction of TCRβ expression in neutrophils and macrophages during malaria infection [12, 13]. Furthermore, an implication of these TCR based myeloid variable immune receptors in several chronic diseases like autoimmune disease [14], chronic periodontitis [15], tuberculosis [9] and atherosclerosis [16] was shown.…”

Section: Introductionmentioning

confidence: 99%

Circulating monocytes and tumor‐associated macrophages express recombined immunoglobulins in glioblastoma patients

Busch

Talamini

Brenner

et al. 2019

Clinical & Translational Med

View full text Add to dashboard Cite

Background Glioblastoma is the most common and malignant brain tumor in adults. Glioblastoma is usually fatal 12–15 months after diagnosis and the current possibilities in therapy are mostly only palliative. Therefore, new forms of diagnosis and therapy are urgently needed. Since tumor-associated macrophages are key players in tumor progression and survival there is large potential in investigating their immunological characteristics in glioblastoma patients. Recent evidence shows the expression of variable immunoglobulins and TCRαβ in subpopulations of monocytes, in vitro polarized macrophages and macrophages in the tumor microenvironment. We set out to investigate the immunoglobulin sequences of circulating monocytes and tumor-associated macrophages from glioblastoma patients to evaluate their potential as novel diagnostic or therapeutic targets. Results We routinely find consistent expression of immunoglobulins in tumor-associated macrophages (TAM) and circulating monocytes from all glioblastoma patients analyzed in this study. However, the immunoglobulin repertoires of circulating monocytes and TAM are generally more restricted compared to B cells. Furthermore, the immunoglobulin expression in the macrophage populations negatively correlates with the tumor volume. Interestingly, the comparison of somatic mutations, V-chain usage, CDR3-length and the distribution of used heavy chain genes on the locus of chromosome 14 of the immunoglobulins from myeloid to B cells revealed virtually no differences. Conclusions The investigation of the immunoglobulin repertoires from TAM and circulating monocytes in glioblastoma-patients revealed a negative correlation to the tumor volume, which could not be detected in the immunoglobulin repertoires of the patients’ B lymphocytes. Furthermore, the immunoglobulin repertoires of monocytes were more diverse than the repertoires of the macrophages in the tumor microenvironment from the same patients suggesting a tumor-specific immune response which could be advantageous for the use as diagnostic or therapeutic target. Electronic supplementary material The online version of this article (10.1186/s40169-019-0235-8) contains supplementary material, which is available to authorized users.

show abstract

“…Meanwhile, the authors also revealed that infection of macrophages from healthy individuals with mycobacteria triggered formation of clusters that express restricted TCR Vβ repertoires 48 . Additionally, several studies have also observed the existence of the TCR + macrophages/monocytes and veri ed by different approaches in human peripheral blood, tumor microenvironment, artery, spleen and the bone marrow 49,50,51,52,53,54 . All these studies demonstrated the existence of macrophages/monocytes with TCRαβ or TCRδγ in health and diseased human or murine tissue.…”

Section: Discussionmentioning

confidence: 94%

A Single-Cell Immune Atlas of Triple Negative Breast Cancer Reveals Novel Immune Cell Subsets

Qiu

Hong

Zhuang

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Triple-negative breast cancer (TNBC) represents the most aggressive breast cancer subtype, which recently attracts great interest for immune therapeutic development. In this context, in-depth understanding of TNBC immune landscape is highly demanded.Results: Here we report full-length single-cell RNA sequencing results of 9683 tumor-infiltrated immune cells isolated from 14 treatment naïve TNBC tumors, where 22 immune cell subsets, including T cells, macrophages, B cells, and DCs have been characterized. We identify a new T cell subset, CD8+CXCL8+ T cell, which associates with poor survival, and a subset of “pre-exhaustion” T cell cluster, which is predictive of favorable prognosis. A novel immune cell subset comprised of TCR+ macrophages, is found to be widely distributed in TNBC tumors. Further analyses reveal an up-regulation of molecules associated with TCR signaling and cytotoxicity in these immune cells.Conclusions: Altogether, our study provides a valuable resource to understand the immune ecosystem of TNBC. The novel immune cell subsets reported herein might be functionally important in cancer immunity. These data will be helpful for the immunotherapeutic strategy design of this disease.

show abstract

TCRβ Combinatorial Immunoreceptor Expression by Neutrophils Correlates with Parasite Burden and Enhanced Phagocytosis during a Plasmodium berghei ANKA Malaria Infection

Cited by 12 publications

References 27 publications

Trilineage Sequencing Reveals Complex TCRβ Transcriptomes in Neutrophils and Monocytes Alongside T Cells

Trilineage Sequencing Reveals Complex TCRβ Transcriptomes in Neutrophils and Monocytes Alongside T Cells

Circulating monocytes and tumor‐associated macrophages express recombined immunoglobulins in glioblastoma patients

A Single-Cell Immune Atlas of Triple Negative Breast Cancer Reveals Novel Immune Cell Subsets

Contact Info

Product

Resources

About