Cathepsins in Bacteria-Macrophage Interaction: Defenders or Victims of Circumstance?

Macrophages are the first encounters of invading bacteria and are responsible for engulfing and digesting pathogens through phagocytosis leading to initiation of the innate inflammatory response. Intracellular digestion occurs through a close relationship between phagocytic/endocytic and lysosomal pathways, in which proteolytic enzymes, such as cathepsins, are involved. The presence of cathepsins in the endo-lysosomal compartment permits direct interaction with and killing of bacteria, and may contribute to processing of bacterial antigens for presentation, an event necessary for the induction of antibacterial adaptive immune response. Therefore, it is not surprising that bacteria can control the expression and proteolytic activity of cathepsins, including their inhibitors – cystatins, to favor their own intracellular survival in macrophages. In this review, we summarize recent developments in defining the role of cathepsins in bacteria-macrophage interaction and describe important strategies engaged by bacteria to manipulate cathepsin expression and activity in macrophages. Particularly, we focus on specific bacterial species due to their clinical relevance to humans and animal health, i.e., Mycobacterium, Mycoplasma, Staphylococcus, Streptococcus, Salmonella, Shigella, Francisella, Chlamydia, Listeria, Brucella, Helicobacter, Neisseria, and other genera.

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The role of epigenetic modifications for the pathogenesis of Crohn's disease

Clinical Epigenetics ◽

10.1186/s13148-021-01089-3 ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

M. Hornschuh ◽

E. Wirthgen ◽

M. Wolfien ◽

K. P. Singh ◽

O. Wolkenhauer ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Adaptive Immune Response ◽

Adaptive Immune ◽

Bowel Diseases ◽

Inflammatory Bowel ◽

New Biomarkers ◽

Insight Into ◽

Specific Evaluation

AbstractEpigenetics has become a promising field for finding new biomarkers and improving diagnosis, prognosis, and drug response in inflammatory bowel disease. The number of people suffering from inflammatory bowel diseases, especially Crohn's disease, has increased remarkably. Crohn's disease is assumed to be the result of a complex interplay between genetic susceptibility, environmental factors, and altered intestinal microbiota, leading to dysregulation of the innate and adaptive immune response. While many genetic variants have been identified to be associated with Crohn's disease, less is known about the influence of epigenetics in the pathogenesis of this disease. In this review, we provide an overview of current epigenetic studies in Crohn's disease. In particular, we enable a deeper insight into applied bioanalytical and computational tools, as well as a comprehensive update toward the cell-specific evaluation of DNA methylation and histone modifications.

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IMMU-22. THE IMPACT OF MICROGLIA MODULATION ON GBM PROGRESSION IN SYNGENEIC MOUSE MODELS

Neuro-Oncology ◽

10.1093/neuonc/noab196.381 ◽

2021 ◽

Vol 23 (Supplement_6) ◽

pp. vi96-vi96

Author(s):

Marie-Françoise Ritz ◽

Tala Shekarian ◽

Tomás A Martins ◽

Philip Schmassmann ◽

Gregor Hutter

Keyword(s):

Mouse Models ◽

Tumor Development ◽

Adaptive Immune Response ◽

Tamoxifen Treatment ◽

Mouse Strains ◽

Intracerebral Injection ◽

Adaptive Immune ◽

Tumor Immune Microenvironment ◽

The Impact

Abstract BACKGROUND The tumor immune microenvironment (TME) of Glioblastoma consists of almost myeloid-derived macrophages and microglia called TAMs. We have shown that the disruption of CD47-Sirpα-axis induces an antitumor activity of TAMs against GBM in immune-deficient mice, through increases of phagocytosis of tumor cells by TAMs. We have aimed to study the role of microglia and its activation/depletion on GBM progression, in the syngeneic GBM model in immune-competent mice. We have studied the interplay of innate and adaptive immune response after activation and depletion of microglia and the effect on tumor progression and outcome of the mice. MATERIAL AND METHODS We used different colonies of genetically modified immunocompetent mouse strains to genetically activate/deplete microglia in the tumor context. We generated Sall1 CreERT2/fl mice and Cre-negative littermates. The application of Tamoxifen in this constellation leads to the excision of the transcription factor Sall1 and subsequent enhanced microglia activity. Conversely, we generated Sall1 CreERT2 x Csf1r fl/fl animals and the respective heterozygous and Cre-negative littermates in which Tamoxifen treatment leads to inactivation of microglia through the deletion of Csf1r. Glioblastoma tumors were induced by intracerebral injection of GL261, CT2A, or retrovirus-induced PDGF-Akt in pups and Tamoxifen treatment was started once the tumors were detected. RESULTS We observed a survival advantage in tumor-bearing mice after activation of microglia in Sall1 CreERT/fl animals compared to Cre-negative littermates. Genetic depletion of microglia in this model resulted in a shorter lifespan in microglia-depleted animals compared to Cre-negative littermates. Furthermore, the iTME in these tumors is subjected to scRNAseq analysis to identify mechanistic insights. CONCLUSION Microglia are important players in tumor development and progression of glioblastoma in mouse models. These cells may be targeted in future immunotherapeutic approaches for patients.

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The role of the T-helper/T-suppressor ratio in the adaptive immune response: a dynamical model

Journal of Physics A Mathematical and Theoretical ◽

10.1088/1751-8121/aaed5e ◽

2018 ◽

Vol 51 (50) ◽

pp. 505602 ◽

Cited By ~ 1

Author(s):

A Annibale ◽

L A Dziobek-Garrett ◽

H Tari

Keyword(s):

Immune Response ◽

Adaptive Immune Response ◽

Dynamical Model ◽

T Helper ◽

Adaptive Immune

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The Pathogenic Role of the Adaptive Immune Response to Modified LDL in Diabetes

Frontiers in Endocrinology ◽

10.3389/fendo.2012.00076 ◽

2012 ◽

Vol 3 ◽

Cited By ~ 8

Author(s):

Gabriel Virella ◽

Maria F. Lopes-Virella

Keyword(s):

Immune Response ◽

Adaptive Immune Response ◽

Pathogenic Role ◽

Adaptive Immune ◽

Modified Ldl

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Pattern Recognition Proteins: First Line of Defense Against Coronaviruses

Frontiers in Immunology ◽

10.3389/fimmu.2021.652252 ◽

2021 ◽

Vol 12 ◽

Author(s):

Carlos A. Labarrere ◽

Ghassan S. Kassab

Keyword(s):

Immune Response ◽

Pattern Recognition ◽

Global Economy ◽

Rna Viruses ◽

Severe Disease ◽

Adaptive Immune Response ◽

Adaptive Immune ◽

Recognition Protein ◽

Pattern Recognition Protein

The rapid outbreak of COVID-19 caused by the novel coronavirus SARS-CoV-2 in Wuhan, China, has become a worldwide pandemic affecting almost 204 million people and causing more than 4.3 million deaths as of August 11 2021. This pandemic has placed a substantial burden on the global healthcare system and the global economy. Availability of novel prophylactic and therapeutic approaches are crucially needed to prevent development of severe disease leading to major complications both acutely and chronically. The success in fighting this virus results from three main achievements: (a) Direct killing of the SARS-CoV-2 virus; (b) Development of a specific vaccine, and (c) Enhancement of the host’s immune system. A fundamental necessity to win the battle against the virus involves a better understanding of the host’s innate and adaptive immune response to the virus. Although the role of the adaptive immune response is directly involved in the generation of a vaccine, the role of innate immunity on RNA viruses in general, and coronaviruses in particular, is mostly unknown. In this review, we will consider the structure of RNA viruses, mainly coronaviruses, and their capacity to affect the lungs and the cardiovascular system. We will also consider the effects of the pattern recognition protein (PRP) trident composed by (a) Surfactant proteins A and D, mannose-binding lectin (MBL) and complement component 1q (C1q), (b) C-reactive protein, and (c) Innate and adaptive IgM antibodies, upon clearance of viral particles and apoptotic cells in lungs and atherosclerotic lesions. We emphasize on the role of pattern recognition protein immune therapies as a combination treatment to prevent development of severe respiratory syndrome and to reduce pulmonary and cardiovascular complications in patients with SARS-CoV-2 and summarize the need of a combined therapeutic approach that takes into account all aspects of immunity against SARS-CoV-2 virus and COVID-19 disease to allow mankind to beat this pandemic killer.

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TH17 cells expressing CD146 are significantly increased in patients with Systemic sclerosis

Scientific Reports ◽

10.1038/s41598-019-54132-y ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 3

Author(s):

Amira Gabsi ◽

Xavier Heim ◽

Akram Dlala ◽

Asma Gati ◽

Haifa Sakhri ◽

...

Keyword(s):

Systemic Sclerosis ◽

Th17 Cells ◽

Vascular System ◽

Adaptive Immune Response ◽

Autoimmune Disorder ◽

Soluble Form ◽

Adaptive Immune ◽

Th17 Lymphocytes

AbstractSystemic sclerosis (SSc) is an autoimmune disorder characterized by vascular damage, excessive fibrosis and abnormal T cells immune-regulation. CD146 is an adhesion molecule essentially expressed in the vascular system, but also on TH17 lymphocytes. In view of the recently described role of CD146 in SSc, we hypothesized an involvement of CD146 positive TH17 cells in this disease. Compared to healthy controls, we showed that both soluble form of CD146 (sCD146), and IL17A levels were increased in patients with SSc with a positive correlation between both factors. A significant increase in TH17 cells attested by an increase of RORγT, IL17A mRNA and CD4+ IL17A+ cell was observed in patients with SSc. Interestingly, the percentage of TH17 cells expressing CD146 was higher in patients with SSc and inversely correlated with pulmonary fibrosis. In vitro experiments showed an augmentation of the percentage of TH17 cells expressing CD146 after cell treatment with sCD146, suggesting that, in patients the increase of this sub-population could be the consequence of the sCD146 increase in serum. In conclusion, TH17 cells expressing CD146 could represent a new component of the adaptive immune response, opening the way for the generation of new tools for the management of SSc.

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Retraction of: Reciprocal role of hBD2 and hBD3 on the adaptive immune response by measuring T lymphocyte proliferation in terms of CD4 and CCR6 expression

Hormone Molecular Biology and Clinical Investigation ◽

10.1515/hmbci-2018-9001 ◽

2018 ◽

Vol 36 (3) ◽

Keyword(s):

Immune Response ◽

T Lymphocyte ◽

Lymphocyte Proliferation ◽

Adaptive Immune Response ◽

Adaptive Immune ◽

T Lymphocyte Proliferation

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Regulation of dendritic cell migration and adaptive immune response by leukotriene B4 receptors: a role for LTB4 in up-regulation of CCR7 expression and function

Blood ◽

10.1182/blood-2006-02-003665 ◽

2006 ◽

Vol 109 (2) ◽

pp. 626-631 ◽

Cited By ~ 83

Author(s):

Annalisa Del Prete ◽

Wen-Hai Shao ◽

Stefania Mitola ◽

Giuseppe Santoro ◽

Silvano Sozzani ◽

...

Keyword(s):

Gene Array ◽

Adaptive Immune Response ◽

Leukotriene B4 ◽

Contact Hypersensitivity ◽

Mrna Levels ◽

Peripheral Tissues ◽

Ccr7 Expression ◽

Adaptive Immune

Abstract Trafficking of dendritic cells (DCs) to peripheral tissues and to secondary lymphoid organs depends on chemokines and lipid mediators. Here, we show that bone marrow–derived DCs (BM-DCs) express functional leukotriene B4 (LTB4) receptors as observed in dose-dependent chemotaxis and calcium mobilization responses. LTB4, at low concentrations, promoted the migration of immature and mature DCs to CCL19 and CCL21, which was associated with a rapid (30-minute) increase of CCR7 expression at the membrane level. At longer incubation times (6 hours), gene array analysis revealed a promoting role of LTB4, showing a significant increase of CCR7 and CCL19 mRNA levels. BM-DCs cultured from BLT1−/− or BLT1/2−/− mice showed a normal phenotype, but in vivo BLT1/2−/−DCs showed dramatic decrease in migration to the draining lymph nodes relative to wild-type (WT) DCs. Consistent with these observations, BLT1/2−/− mice showed a reduced response in a model of 2,4-dinitro-fluorobenzene (DNFB)–induced contact hypersensitivity. Adoptive transfer of 2,4-dinitrobenzene sulfonic acid (DNBS)–pulsed DCs directly implicated the defect in DC migration to lymph node with the defect in contact hypersensitivity. These results provide strong evidence for a role of LTB4 in regulating DC migration and the induction of adaptive immune responses.

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