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Article ; Online: Targeted transcriptomic analyses of RNA isolated from formalin-fixed and paraffin-embedded human menisci.

Monibi, Farrah A / Pannellini, Tania / Croen, Brett / Otero, Miguel / Warren, Russell / Rodeo, Scott A

Journal of orthopaedic research : official publication of the Orthopaedic Research Society

2021 Volume 40, Issue 5, Page(s) 1104–1112

Abstract: Formalin-fixed and paraffin-embedded (FFPE) biospecimens are a valuable and widely-available resource for diagnostic and research applications. With biobanks of tissue samples available in many institutions, FFPE tissues could prove to be a valuable ... ...

Abstract	Formalin-fixed and paraffin-embedded (FFPE) biospecimens are a valuable and widely-available resource for diagnostic and research applications. With biobanks of tissue samples available in many institutions, FFPE tissues could prove to be a valuable resource for translational orthopaedic research. The purpose of this study was to characterize the molecular profiles and degree of histologic degeneration on archival fragments of FFPE human menisci obtained during arthroscopic partial meniscectomy. We used FFPE menisci for multiplexed gene expression analysis using the NanoString nCounter® platform, and for histological assessment using a quantitative scoring system. In total, 17 archival specimens were utilized for integrated histologic and molecular analyses. The median patient age was 22 years (range: 14-62). We found that the genes with the highest normalized counts were those typically expressed in meniscal fibrocartilage. Gene expression differences were identified in patient cohorts based on age (≤40 years), including genes associated with the extracellular matrix and tissue repair. The majority of samples showed mild to moderate histologic degeneration. Based on these data, we conclude that FFPE human menisci can be effectively utilized for molecular evaluation following a storage time as long as 11 years. Statement of Clinical Significance: The integration of histological and transcriptomic analyses described in this study will be useful for future studies investigating the basis for biological classification of meniscus specimens in patients. Further exploration into the genes and pathways uncovered by this study may suggest targets for biomarker discovery and identify patients at greater risk for osteoarthritis once the meniscus is torn.
MeSH term(s)	Adolescent ; Adult ; Formaldehyde ; Gene Expression Profiling ; Humans ; Meniscus ; Middle Aged ; Paraffin Embedding ; RNA/analysis ; Tissue Fixation ; Transcriptome ; Young Adult
Chemical Substances	Formaldehyde (1HG84L3525) ; RNA (63231-63-0)
Language	English
Publishing date	2021-08-18
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	605542-4
ISSN	1554-527X ; 0736-0266
ISSN (online)	1554-527X
ISSN	0736-0266
DOI	10.1002/jor.25153
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Zs.A 1879: Show issues

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Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

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Article ; Online: Histologic and molecular features in pathologic human menisci from knees with and without osteoarthritis.

Monibi, Farrah A / Pannellini, Tania / Otero, Miguel / Warren, Russell F / Rodeo, Scott A

Journal of orthopaedic research : official publication of the Orthopaedic Research Society

2021 Volume 40, Issue 2, Page(s) 504–512

Abstract: The objective of this study was to evaluate histologic and molecular features of meniscus degeneration in cohorts of patients with and without osteoarthritis (OA) of the knee. Menisci were obtained from patients undergoing total knee arthroplasty for OA ( ...

Abstract	The objective of this study was to evaluate histologic and molecular features of meniscus degeneration in cohorts of patients with and without osteoarthritis (OA) of the knee. Menisci were obtained from patients undergoing total knee arthroplasty for OA (TKA) or arthroscopic partial meniscectomy (APM) for a torn knee meniscus. Degenerative meniscal tears were among the most common tear type in the APM group based on the pattern. Using an integrative workflow for molecular evaluation of formalin-fixed and paraffin-embedded tissues, human menisci underwent blinded histologic evaluation and NanoString gene expression analyses. Histology revealed increased proteoglycan content in TKA menisci compared to APM menisci, but otherwise no significant differences in the total pathology score or sub-scores between patients based on age or cohort. NanoString analyses revealed differential expression of genes primarily associated with the PI3K-AKT signaling pathway, cell cycle, and apoptosis. These data provide new insights into histological and molecular features of meniscus degeneration in patients with and without knee OA. Histologic assessment of menisci showed similar severity of overall degeneration between cohorts, but there were differences at the molecular level. The dysregulated pathways identified in this study could contribute to early-onset meniscus degeneration, or to a predisposition to meniscus tears and subsequent knee OA. Further studies that validate genes and pathways uncovered in this study will allow us to evaluate novel approaches to assess and treat meniscal degeneration.
MeSH term(s)	Arthroscopy ; Humans ; Knee Injuries/pathology ; Meniscectomy ; Menisci, Tibial/pathology ; Menisci, Tibial/surgery ; Meniscus/pathology ; Osteoarthritis, Knee/pathology ; Phosphatidylinositol 3-Kinases
Language	English
Publishing date	2021-04-19
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	605542-4
ISSN	1554-527X ; 0736-0266
ISSN (online)	1554-527X
ISSN	0736-0266
DOI	10.1002/jor.25047
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Article: Lymphatic Dysfunction Models an Autoimmune Emphysema Phenotype of Chronic Obstructive Pulmonary Disease.

Summers, Barbara / Kim, Kihwan / Lu, Tyler M / Houghton, Sean / Trivedi, Anjali / Quintero, Joselyn Rojas / Cala-Garcia, Juan / Pannellini, Tania / Polverino, Francesca / Lis, Raphaël / Reed, Hasina Outtz

bioRxiv : the preprint server for biology

2023

Abstract: Chronic Obstructive Pulmonary Disease (COPD) is a heterogeneous disease that is characterized by many clinical phenotypes. One such phenotype of COPD is defined by emphysema, pathogenic lung tertiary lymphoid organs (TLOs), and autoantibody production. ... ...

Abstract	Chronic Obstructive Pulmonary Disease (COPD) is a heterogeneous disease that is characterized by many clinical phenotypes. One such phenotype of COPD is defined by emphysema, pathogenic lung tertiary lymphoid organs (TLOs), and autoantibody production. We have previously shown that lymphatic dysfunction can cause lung TLO formation and lung injury in mice. We now sought to uncover whether underlying lymphatic dysfunction may be a driver of lung injury in cigarette smoke (CS)-induced COPD. We found that lung TLOs in mice with lymphatic dysfunction produce autoantibodies and are associated with a lymphatic endothelial cell subtype that expresses antigen presentation genes. Mice with underlying lymphatic dysfunction develop increased emphysema after CS exposure, with increased size and activation of TLOs. CS further increased autoantibody production in mice with lymphatic dysfunction. B-cell blockade prevented TLO formation and decreased lung injury after CS in mice with lymphatic dysfunction. Using tissue from human COPD patients, we also found evidence of a lymphatic gene signature that was specific to patients with emphysema and prominent TLOs compared to COPD patients without emphysema. Taken together, these data suggest that lymphatic dysfunction may underlie lung injury in a subset of COPD patients with an autoimmune emphysema phenotype.
Language	English
Publishing date	2023-11-02
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.10.31.564938
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Article: Clinical and Histological Features of Prosthetic Joint Infections May Differ in Patients With Inflammatory Arthritis and Osteoarthritis.

Sculco, Peter / Kapadia, Milan / Moezinia, Carine J / Mannstadt, Insa / Miller, Andy O / Donlin, Laura / Henry, Michael / Russell, Linda / Figgie, Mark / Nocon, Allina / Pannellini, Tania / Goodman, Susan M

HSS journal : the musculoskeletal journal of Hospital for Special Surgery

2023 Volume 19, Issue 2, Page(s) 146–153

Abstract: Background: ...

Abstract	Background:
Language	English
Publishing date	2023-02-13
Publishing country	United States
Document type	Journal Article
ZDB-ID	2250601-9
ISSN	1556-3324 ; 1556-3316
ISSN (online)	1556-3324
ISSN	1556-3316
DOI	10.1177/15563316231153395
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Zs.A 6398: Show issues

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Article ; Online: Transcriptomic and epigenomic analyses uncovered Lrrc15 as a contributing factor to cartilage damage in osteoarthritis.

Singh, Purva / Wang, Mengying / Mukherjee, Piali / Lessard, Samantha G / Pannellini, Tania / Carballo, Camila B / Rodeo, Scott A / Goldring, Mary B / Otero, Miguel

Scientific reports

2021 Volume 11, Issue 1, Page(s) 21107

Abstract: In osteoarthritis (OA), articular chondrocytes display phenotypic and functional changes associated with epigenomic alterations. These changes contribute to the disease progression, which is characterized by dysregulated reparative processes and abnormal ...

Abstract	In osteoarthritis (OA), articular chondrocytes display phenotypic and functional changes associated with epigenomic alterations. These changes contribute to the disease progression, which is characterized by dysregulated reparative processes and abnormal extracellular matrix remodeling leading to cartilage degradation. Recent studies using a murine model of posttraumatic OA highlighted the contribution of changes in DNA hydroxymethylation (5hmC) to OA progression. Here, we integrated transcriptomic and epigenomic analyses in cartilage after induction of OA to show that the structural progression of OA is accompanied by early transcriptomic and pronounced DNA methylation (5mC) changes in chondrocytes. These changes accumulate over time and are associated with recapitulation of developmental processes, including cartilage development, chondrocyte hypertrophy, and ossification. Our integrative analyses also uncovered that Lrrc15 is differentially methylated and expressed in OA cartilage, and that it may contribute to the functional and phenotypic alterations of chondrocytes, likely coordinating stress responses and dysregulated extracellular matrix remodeling.
MeSH term(s)	Animals ; Cartilage, Articular/metabolism ; DNA Methylation ; Epigenome ; Epigenomics ; Gene Expression Profiling ; Humans ; Male ; Membrane Proteins/biosynthesis ; Membrane Proteins/genetics ; Mice ; Osteoarthritis/genetics ; Osteoarthritis/metabolism ; Transcriptome
Chemical Substances	LRRC15 protein, human ; Lrrc15 protein, mouse ; Membrane Proteins
Language	English
Publishing date	2021-10-26
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-021-00269-8
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Article ; Online: Noncytotoxic Inhibition of the Immunoproteasome Regulates Human Immune Cells In Vitro and Suppresses Cutaneous Inflammation in the Mouse.

Ah Kioon, Marie Dominique / Pierides, Michael / Pannellini, Tania / Lin, Gang / Nathan, Carl F / Barrat, Franck J

Journal of immunology (Baltimore, Md. : 1950)

2021 Volume 206, Issue 7, Page(s) 1631–1641

Abstract: Inhibitors of the immunoproteasome (i-20S) have shown promise in mouse models of autoimmune diseases and allograft rejection. In this study, we used a novel inhibitor of the immunoproteasome, PKS3053, that is reversible, noncovalent, tight-binding, and ... ...

Abstract	Inhibitors of the immunoproteasome (i-20S) have shown promise in mouse models of autoimmune diseases and allograft rejection. In this study, we used a novel inhibitor of the immunoproteasome, PKS3053, that is reversible, noncovalent, tight-binding, and highly selective for the β5i subunit of the i-20S to evaluate the role that i-20S plays in regulating immune responses in vitro and in vivo. In contrast to irreversible, less-selective inhibitors, PKS3053 did not kill any of the primary human cell types tested, including plasmacytoid dendritic cells, conventional dendritic cells, macrophages, and T cells, all of which expressed genes encoding both the constitutive proteasome (c-20S) and i-20S. PKS3053 reduced TLR-dependent activation of plasmacytoid dendritic cells, decreasing their maturation and IFN-α response and reducing their ability to activate allogenic T cells. In addition, PKS3053 reduced T cell proliferation directly and inhibited TLR-mediated activation of conventional dendritic cells and macrophages. In a mouse model of skin injury that shares some features of cutaneous lupus erythematosus, blocking i-20S decreased inflammation, cellular infiltration, and tissue damage. We conclude that the immunoproteasome is involved in the activation of innate and adaptive immune cells, that their activation can be suppressed with an i-20S inhibitor without killing them, and that selective inhibition of β5i holds promise as a potential therapy for inflammatory skin diseases such as psoriasis, cutaneous lupus erythematosus, and systemic sclerosis.
MeSH term(s)	Animals ; Cell Movement ; Cells, Cultured ; Cytotoxicity, Immunologic ; Dendritic Cells/drug effects ; Dendritic Cells/immunology ; Disease Models, Animal ; Female ; Humans ; Inflammation/drug therapy ; Lupus Erythematosus, Cutaneous/drug therapy ; Lymphocyte Activation ; Macrophages/drug effects ; Macrophages/immunology ; Mice ; Mice, Inbred C57BL ; Proteasome Endopeptidase Complex/metabolism ; Proteasome Inhibitors/therapeutic use ; Skin/pathology ; T-Lymphocytes/drug effects ; T-Lymphocytes/immunology
Chemical Substances	Proteasome Inhibitors ; Proteasome Endopeptidase Complex (EC 3.4.25.1)
Language	English
Publishing date	2021-03-05
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	3056-9
ISSN	1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
ISSN (online)	1550-6606
ISSN	0022-1767 ; 1048-3233 ; 1047-7381
DOI	10.4049/jimmunol.2000951
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Ud II Zs.37: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.MG 28: Show issues

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Article ; Online: Spatial mapping of human hematopoiesis at single-cell resolution reveals aging-associated topographic remodeling.

Blood

2023 Volume 142, Issue 26, Page(s) 2282–2295

Abstract: Abstract: The spatial anatomy of hematopoiesis in the bone marrow (BM) has been extensively studied in mice and other preclinical models, but technical challenges have precluded a commensurate exploration in humans. Institutional pathology archives ... ...

Abstract	Abstract: The spatial anatomy of hematopoiesis in the bone marrow (BM) has been extensively studied in mice and other preclinical models, but technical challenges have precluded a commensurate exploration in humans. Institutional pathology archives contain thousands of paraffinized BM core biopsy tissue specimens, providing a rich resource for studying the intact human BM topography in a variety of physiologic states. Thus, we developed an end-to-end pipeline involving multiparameter whole tissue staining, in situ imaging at single-cell resolution, and artificial intelligence-based digital whole slide image analysis and then applied it to a cohort of disease-free samples to survey alterations in the hematopoietic topography associated with aging. Our data indicate heterogeneity in marrow adipose tissue (MAT) content within each age group and an inverse correlation between MAT content and proportions of early myeloid and erythroid precursors, irrespective of age. We identify consistent endosteal and perivascular positioning of hematopoietic stem and progenitor cells (HSPCs) with medullary localization of more differentiated elements and, importantly, uncover new evidence of aging-associated changes in cellular and vascular morphologies, microarchitectural alterations suggestive of foci with increased lymphocytes, and diminution of a potentially active megakaryocytic niche. Overall, our findings suggest that there is topographic remodeling of human hematopoiesis associated with aging. More generally, we demonstrate the potential to deeply unravel the spatial biology of normal and pathologic human BM states using intact archival tissue specimens.
MeSH term(s)	Humans ; Mice ; Animals ; Artificial Intelligence ; Hematopoietic Stem Cells/pathology ; Bone Marrow/pathology ; Hematopoiesis/physiology ; Aging
Language	English
Publishing date	2023-09-29
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80069-7
ISSN	1528-0020 ; 0006-4971
ISSN (online)	1528-0020
ISSN	0006-4971
DOI	10.1182/blood.2023021280
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Uh III Zs.140: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.MO 364: Show issues

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Article ; Online: Rheumatoid Arthritis Synovial Inflammation Quantification Using Computer Vision.

Guan, Steven / Mehta, Bella / Slater, David / Thompson, James R / DiCarlo, Edward / Pannellini, Tania / Pearce-Fisher, Diyu / Zhang, Fan / Raychaudhuri, Soumya / Hale, Caryn / Jiang, Caroline S / Goodman, Susan / Orange, Dana E

ACR open rheumatology

2022 Volume 4, Issue 4, Page(s) 322–331

Abstract: Objective: We quantified inflammatory burden in rheumatoid arthritis (RA) synovial tissue by using computer vision to automate the process of counting individual nuclei in hematoxylin and eosin images.: Methods: We adapted and applied computer vision ...

Abstract	Objective: We quantified inflammatory burden in rheumatoid arthritis (RA) synovial tissue by using computer vision to automate the process of counting individual nuclei in hematoxylin and eosin images. Methods: We adapted and applied computer vision algorithms to quantify nuclei density (count of nuclei per unit area of tissue) on synovial tissue from arthroplasty samples. A pathologist validated algorithm results by labeling nuclei in synovial images that were mislabeled or missed by the algorithm. Nuclei density was compared with other measures of RA inflammation such as semiquantitative histology scores, gene-expression data, and clinical measures of disease activity. Results: The algorithm detected a median of 112,657 (range 8,160-821,717) nuclei per synovial sample. Based on pathologist-validated results, the sensitivity and specificity of the algorithm was 97% and 100%, respectively. The mean nuclei density calculated by the algorithm was significantly higher (P < 0.05) in synovium with increased histology scores for lymphocytic inflammation, plasma cells, and lining hyperplasia. Analysis of RNA sequencing identified 915 significantly differentially expressed genes in correlation with nuclei density (false discovery rate is less than 0.05). Mean nuclei density was significantly higher (P < 0.05) in patients with elevated levels of C-reactive protein, erythrocyte sedimentation rate, rheumatoid factor, and cyclized citrullinated protein antibody. Conclusion: Nuclei density is a robust measurement of inflammatory burden in RA and correlates with multiple orthogonal measurements of inflammation.
Language	English
Publishing date	2022-01-10
Publishing country	United States
Document type	Journal Article
ISSN	2578-5745
ISSN (online)	2578-5745
DOI	10.1002/acr2.11381
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Article ; Online: Interleukin-13 Receptor α1-Mediated Signaling Regulates Age-Associated/Autoimmune B Cell Expansion and Lupus Pathogenesis.

Chen, Zhu / Flores Castro, Danny / Gupta, Sanjay / Phalke, Swati / Manni, Michela / Rivera-Correa, Juan / Jessberger, Rolf / Zaghouani, Habib / Giannopoulou, Eugenia / Pannellini, Tania / Pernis, Alessandra B

Arthritis & rheumatology (Hoboken, N.J.)

2022 Volume 74, Issue 9, Page(s) 1544–1555

Abstract: Objective: Age-associated/autoimmune B cells (ABCs) are an emerging B cell subset with aberrant expansion in systemic lupus erythematosus. ABC generation and differentiation exhibit marked sexual dimorphism, and Toll-like receptor 7 (TLR-7) engagement ... ...

Abstract	Objective: Age-associated/autoimmune B cells (ABCs) are an emerging B cell subset with aberrant expansion in systemic lupus erythematosus. ABC generation and differentiation exhibit marked sexual dimorphism, and Toll-like receptor 7 (TLR-7) engagement is a key contributor to these sex differences. ABC generation is also controlled by interleukin-21 (IL-21) and its interplay with interferon-γ and IL-4. This study was undertaken to investigate whether IL-13 receptor α1 (IL-13Rα1), an X-linked receptor that transmits IL-4/IL-13 signals, regulates ABCs and lupus pathogenesis. Methods: Mice lacking DEF-6 and switch-associated protein 70 (double-knockout [DKO]), which preferentially develop lupus in females, were crossed with IL-13Rα1-knockout mice. IL-13Rα1-knockout male mice were also crossed with Y chromosome autoimmune accelerator (Yaa) DKO mice, which overexpress TLR-7 and develop severe disease. ABCs were assessed using flow cytometry and RNA-Seq. Lupus pathogenesis was evaluated using serologic and histologic analyses. Results: ABCs expressed higher levels of IL-13Rα1 than follicular B cells. The absence of IL-13Rα1 in either DKO female mice or Yaa DKO male mice decreased the accumulation of ABCs, the differentiation of ABCs into plasmablasts, and autoantibody production. Lack of IL-13Rα1 also prolonged survival and delayed the development of tissue inflammation. IL-13Rα1 deficiency diminished in vitro generation of ABCs, an effect that, surprisingly, could be observed in response to IL-21 alone. RNA-Seq revealed that ABCs lacking IL-13Rα1 down-regulated some histologic characteristics of B cells but up-regulated myeloid markers and proinflammatory mediators. Conclusion: Our findings indicate a novel role for IL-13Rα1 in controlling ABC generation and differentiation, suggesting that IL-13Rα1 contributes to these effects by regulating a subset of IL-21-mediated signaling events. These results also suggest that X-linked genes besides TLR7 participate in the regulation of ABCs in lupus.
MeSH term(s)	Animals ; Female ; Interleukin-13/metabolism ; Interleukin-13 Receptor alpha1 Subunit/genetics ; Interleukin-4 ; Lupus Erythematosus, Systemic/genetics ; Lupus Erythematosus, Systemic/metabolism ; Male ; Mice ; Mice, Knockout ; Receptors, Interleukin-13/genetics ; Toll-Like Receptor 7
Chemical Substances	Interleukin-13 ; Interleukin-13 Receptor alpha1 Subunit ; Receptors, Interleukin-13 ; Toll-Like Receptor 7 ; Interleukin-4 (207137-56-2)
Language	English
Publishing date	2022-08-22
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2756371-6
ISSN	2326-5205 ; 2326-5191
ISSN (online)	2326-5205
ISSN	2326-5191
DOI	10.1002/art.42146
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Zs.A 24: Show issues

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Article ; Online: Immune Response to Persistent Staphyloccocus Aureus Periprosthetic Joint Infection in a Mouse Tibial Implant Model.

Sokhi, Upneet K / Xia, Yunwei / Sosa, Branden / Turajane, Kathleen / Nishtala, Sita N / Pannellini, Tania / Bostrom, Mathias P / Carli, Alberto V / Yang, Xu / Ivashkiv, Lionel B

Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research

2022 Volume 37, Issue 3, Page(s) 577–594

Abstract: Staphyloccocus aureus is one of the major pathogens in orthopedic periprosthetic joint infection (PJI), a devastating complication of total joint arthroplasty that often results in chronic and persistent infections that are refractory to antibiotics and ... ...

Abstract	Staphyloccocus aureus is one of the major pathogens in orthopedic periprosthetic joint infection (PJI), a devastating complication of total joint arthroplasty that often results in chronic and persistent infections that are refractory to antibiotics and require surgical interventions. Biofilm formation has been extensively investigated as a reason for persistent infection. The cellular composition, activation status, cytokine profile, and role of the immune response during persistent S. aureus PJI are incompletely understood. In this study, we used histology, multiparametric flow cytometry, and gene expression analysis to characterize the immune response in a clinically relevant orthopedic PJI model. We tested the hypothesis that persistent S. aureus infection induces feedback mechanisms that suppress immune cell activation, thereby affecting the course of infection. Surprisingly, persistent infection was characterized by strikingly high cytokine gene expression indicative of robust activation of multiple components of innate and adaptive immunity, along with ongoing severe neutrophil-dominated inflammation, in infected joint and bone tissues. Activation and expansion of draining lymph nodes and a bone marrow stress granulopoiesis reaction were also maintained during late phase infection. In parallel, feedback mechanisms involving T-cell inhibitory receptors and exhaustion markers, suppressive cytokines, and regulatory T cells were activated and associated with decreased T-cell proliferation and tissue infiltration during the persistent phase of infection. These results identify the cellular and molecular components of the mouse immune response to persistent S. aureus PJI and indicate that neutrophil infiltration, inflammatory cytokine responses, and ongoing lymph node and bone marrow reactions are insufficient to clear infection and that immune effector mechanisms are suppressed by feedback inhibitory pathways. These immune-suppressive mechanisms are associated with diminished T-cell proliferation and tissue infiltration and can be targeted as part of adjuvant immunotherapeutic strategies in combination with debridement of biofilm, antibiotics, and other therapeutic modalities to promote eradication of infection. © 2021 American Society for Bone and Mineral Research (ASBMR).
MeSH term(s)	Animals ; Anti-Bacterial Agents ; Cytokines ; Disease Models, Animal ; Immunity ; Mice ; Prosthesis-Related Infections/drug therapy ; Prosthesis-Related Infections/etiology ; Staphylococcal Infections/drug therapy ; Staphylococcus aureus ; Tibia/transplantation
Chemical Substances	Anti-Bacterial Agents ; Cytokines
Language	English
Publishing date	2022-01-03
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	632783-7
ISSN	1523-4681 ; 0884-0431
ISSN (online)	1523-4681
ISSN	0884-0431
DOI	10.1002/jbmr.4489
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