BoLA class II polymorphism and immune response to Mycobacterium bovis antigens in vitro

1995 ◽  
Vol 112 (1-6) ◽  
pp. 391-400 ◽  
Author(s):  
M. Zanotti Casati ◽  
M. Longeri ◽  
M. Polli ◽  
G. Ceriotti ◽  
G. Poli
Keyword(s):  
Immune Response ◽  
Mycobacterium Bovis ◽  
Class Ii ◽  
Bola Class

scholarly journals Kallikrein 12 Regulates Innate Resistance of Murine Macrophages against Mycobacterium bovis Infection by Modulating Autophagy and Apoptosis

Cells ◽  
2019 ◽  
Vol 8 (5) ◽  
pp. 415 ◽  
Author(s):  
Naveed Sabir ◽  
Tariq Hussain ◽  
Yi Liao ◽  
Jie Wang ◽  
Yinjuan Song ◽  
...  
Keyword(s):  
Immune Response ◽  
Mycobacterium Bovis ◽  
Serine Proteases ◽  
New Paradigm ◽  
Murine Macrophages ◽  
Immune Response Regulation ◽  
The Difference

Mycobacterium bovis (M. bovis) is a member of the Mycobacterium tuberculosis (Mtb) complex causing bovine tuberculosis (TB) and imposing a high zoonotic threat to human health. Kallikreins (KLKs) belong to a subgroup of secreted serine proteases. As their role is established in various physiological and pathological processes, it is likely that KLKs expression may mediate a host immune response against the M. bovis infection. In the current study, we report in vivo and in vitro upregulation of KLK12 in the M. bovis infection. To define the role of KLK12 in immune response regulation of murine macrophages, we produced KLK12 knockdown bone marrow derived macrophages (BMDMs) by using siRNA transfection. Interestingly, the knockdown of KLK12 resulted in a significant downregulation of autophagy and apoptosis in M. bovis infected BMDMs. Furthermore, we demonstrated that this KLK12 mediated regulation of autophagy and apoptosis involves mTOR/AMPK/TSC2 and BAX/Bcl-2/Cytochrome c/Caspase 3 pathways, respectively. Similarly, inflammatory cytokines IL-1β, IL-6, IL-12 and TNF-α were significantly downregulated in KLK12 knockdown macrophages but the difference in IL-10 and IFN-β expression was non-significant. Taken together, these findings suggest that upregulation of KLK12 in M. bovis infected murine macrophages plays a substantial role in the protective immune response regulation by modulating autophagy, apoptosis and pro-inflammatory pathways. To our knowledge, this is the first report on expression and the role of KLK12 in the M. bovis infection and the data may contribute to a new paradigm for diagnosis and treatment of bovine TB.

Immunological relevance of the tumor associated antigen (TAA) COA-1 in colorectal cancer (CRC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 13590-13590
Author(s):  
D. C. Corsi ◽  
C. Maccalli ◽  
M. Ciaparrone ◽  
A. F. Scinto ◽  
G. Cucchiara ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Cd8 T Cells ◽  
Cd4 T Cells ◽  
Specific Antigen ◽  
Class Ii ◽  
Hla Typing ◽  
Class I ◽  
Mhc Molecules

13590 Background: Immunotherapy (IT) in CRC has often produced discouraging results. COA-1 is a new TAA recognized by CD4+ T cells from peripheral blood (PB) of a CRC pt; its immunogenic epitope is presented on the surface of tumor cells in association with DRβ1*1301 or *0402 HLA class II molecules. Our aim is verifying whether an immune response directed against COA-1 mediated by CD4+ T cells can be isolated from PB of CRC pts. To achieve a more efficient anti-tumor response a recognition of a specific antigen by both the CD4+ and CD8+ lymphocytes should be performed; so different epitopes deriving from the processing of the same antigen should be presented to the immune system in association with both class I and class II MHC molecules. We identified a list of COA-1 derived peptides with the calculated score for the binding to HLA-A2, the more common HLA class I molecule within the Caucasian population. A failure in generating COA-1 specific T cells was observed in stage I-II CRC pts. Methods: From Jan 04 to day PB samples from 36 CRC pts (14 stage III/ 22 stage IV) have been collected and the HLA typing has been performed. Pts. expressing HLA DRbβ*0402, HLA DRβ1*1301 or HLA-A2 have been selected to collect other blood drawns and verifying whether an immune response directed against COA-1 could be isolated from their PB. Results: 4 pts were positive for the expression of DRβ1*1301 and 2 for the expression of DRβ1*0402. PB lymphocytes have been in vitro stimulated with the COA-1 derived epitopes and tumor reactivity has been verified. An immune response directed to COA-1 was detected in the PB of these 6 pts; anti-COA-1 CD4+ T cells were in vitro isolated and their cytotoxicity measured by granzyme B release. 9 pts were positive for the expression of HLA-A2 and we are stimulating the lymphocytes isolated from these pts with 6 selected COA-1 derived peptides binding the HLA-A2. We observed specific CD8+ T cells for 2 peptides in 1 pt. Conclusions: Our data identify COA-1 like an immunogenic antigen that can evoke an anti-tumor immune response CD4+ mediated in CRC; the response correlates with disease progression. Experiments are ongoing to evaluate an immune response mediated by both CD4+ and CD8+ T cells. These results will determine whether COA-1 could be used for future protocols of IT in CRC. No significant financial relationships to disclose.

scholarly journals PM2.5 Mediated Alterations In The In Vitro Human Granuloma Resulting In Reactivation Of Mycobacteria

2021 ◽  
Author(s):  
Athisankaran Punniyamurthy ◽  
Sumedha Sharma ◽  
Khushpreet Kaur ◽  
Uma Nahar Saikia ◽  
Ravindra Khaiwal ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Particulate Matter ◽  
Mycobacterium Bovis ◽  
Bacterial Load ◽  
Granuloma Formation ◽  
Human Pbmcs ◽  
Cytokine Levels ◽  
Mycobacterial Antigens

Abstract Exposure to pollutants diminishes the immune response to mycobacterial antigens relevant to contain the infection in the granuloma, thus leading to reactivation of latent bacilli. Present study was therefore designed based on the hypothesis that exposure to particulate matter pollutant PM2.5 affects the granuloma formation and reactivation of latent mycobacterial bacilli contained in the granuloma. For the extraction of PM2.5, based on initial standardizations, teflon filter was selected over the quartz filter. Two different approaches were used to study the effect of PM2.5 on the human PBMCs granuloma formed by Mycobacterium bovis BCG at MOI 0.1. In the first approach, granuloma formed in the presence of PM2.5 was loosely packed and ill-defined with significant downregulation of dormancy associated mycobacterial genes, upregulation of reactivation associated rpfB gene along with a significant increase in TNFα level without any change in the bacterial load in terms of CFUs. In the second approach, PM2.5 treatment of already established human PBMCs granuloma formed with M. bovis BCG also led to its disruption. Although, in these conditions, downregulation of dormancy associated genes was observed but there was also a decrease in the expression of reactivation associated rpfB gene without any change in the cytokine levels. Therefore, it can be inferred that in the presence of PM2.5, there is poor granuloma formation along with a change in mycobacterial gene expression characteristics of active bacilli and alteration in host immune response without any significant changes following treatment of already established granuloma with the pollutant.

scholarly journals Matrix Embedding Alters the Immune Response Against Endothelial Cells In Vitro and In Vivo

Circulation ◽  
2005 ◽  
Vol 112 (9_supplement) ◽  
Author(s):  
Heiko Methe ◽  
Helen M. Nugent ◽  
Adam Groothuis ◽  
Philip Seifert ◽  
Mohamed H. Sayegh ◽  
...  
Keyword(s):  
Immune Response ◽  
Adhesion Molecules ◽  
Mhc Class Ii ◽  
Vascular Diseases ◽  
Metabolic Activation ◽  
Host Immune Response ◽  
Class Ii ◽  
3 Dimensional

Background— Endothelial cell (EC) dysfunction represents the first manifestation of atherosclerotic disease. Restoration of endothelium via seeding or transfection is hampered by local alterations in flow, inflammation, and metabolic activation. Perivascular EC matrix implants are shielded from these forces and still control vascular repair. The host immune response to such implants, however, remains largely unknown. We investigated the effect of embedding of ECs within 3-dimensional matrices on host immune responses in vitro and in vivo. Methods and Results— We compared expression of major histocompatibility complex (MHC), costimulatory, and adhesion molecules by free aortic ECs or ECs embedded in Gelfoam matrices by flow-cytometry. T-cell proliferation was assessed by [ 3 H] thymidine incorporation. Humoral immune response (ELISA and FACS analysis) and cellular (histopathology) infiltration were investigated after subcutaneous injection of free porcine aortic ECs (PAEs) or of a Gelfoam/EC block, or after concomitant injection of PAEs adjacent to Gelfoam in rats. Aortic ECs embedded in Gelfoam expressed lower levels of MHC class II, costimulatory, and adhesion molecules compared with free ECs ( P <0.001), and induced 3-fold less proliferation of human CD4 + T-cells ( P <0.0005). Implantation of a Gelfoam/EC block in rats nearly abrogated the immune response with 1.75- to 9.0-fold downregulation in tumor necrosis factor-α, interleukin-6, monocyte chemotactic protein-1, and PAE-specific immunoglobulin G ( P <0.005) and 3.3- to 4.5-fold reduction in leukocytic tissue infiltration. Injecting PAEs adjacent to Gelfoam induced a significant response comparable to that of free implanted PAEs. Conclusions— Embedding ECs within 3-dimensional matrices alters the host immune response by inhibiting expression of MHC class II, costimulatory, and adhesion molecules, offering the rationale to develop novel therapies for vascular diseases.

Dendritic Cells as a Novel Target for Erythropoietin: Studies in Murine Models.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2417-2417
Author(s):  
Lilach Lifchitz ◽  
Sari Prutchi Sagiv ◽  
Maayan Markovitz ◽  
Moshe Mittelman ◽  
Drorit Newmann
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
Mhc Class Ii ◽  
Surface Expression ◽  
Class Ii ◽  
Mapk Signaling ◽  
Target Cells ◽  
Erythroid Progenitor

Abstract Erythropoietin (EPO) is the major hormone that promotes the proliferation and differentiation of erythroid progenitor cells. Unexpectedly, EPO receptor (EPO-R) was also found on non-erythroid cells; thus leading to the discovery of non-erythroid effects of EPO. Our own previous contribution to that issue was in demonstrating that the immune system is a target for EPO, including both the cellular and humoral immune response types. As yet, the direct target cells for EPO as well as the molecular mechanisms underlying its function as an immunomodulator remain unknown. We first examined lymphocytes as possible candidates, and could not detect any expression of EPO-Rs on these cells. Here, we focused on dendritic cells (DCs), known to initiate immune response as antigen presenting and T cell priming cells. We employed murine bone marrow DCs (BMDCs) and splenic DCs (SDCs) models to determine EPO-R expression, and delineate in-vitro and in-vivo effects of EPO via these cells. We found that BMDCs express EPO-R mRNA, as detected by RT-PCR. In vitro stimulation of the BMDCs with recombinant human EPO (rHuEPO) activated the NFkB and MAPK signaling pathways, and induced a higher surface expression of CD80, CD86 and MHC class II. These data are reinforced by in vivo experiments, showing that rHuEPO injection into naïve mice led to an increase in the SDC population and in the cell surface expression of CD80, CD86 and MHC class II markers. These novel findings implicate the significance of the multifunctional role of EPO in the hematopoietic and immune systems, and may lead to its further clinical applications as an immunomodulator.

BoLA class I polymorphism and in vitro immune response to M. bovis antigens

1993 ◽  
Vol 110 (1-6) ◽  
pp. 335-345 ◽  
Author(s):  
M. Longeri ◽  
M. Polli ◽  
W. Ponti ◽  
M. Zanotti
Keyword(s):  
Immune Response ◽  
Class I ◽  
In Vitro Immune Response ◽  
Bola Class

scholarly journals Development of a Guinea Pig Immune Response-Related Microarray and Its Use To Define the Host Response following Mycobacterium bovis BCG Vaccination

2006 ◽  
Vol 74 (2) ◽  
pp. 1436-1441 ◽  
Author(s):  
Julia A. Tree ◽  
Michael J. Elmore ◽  
Sajid Javed ◽  
Ann Williams ◽  
Philip D. Marsh
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Immune Responses ◽  
Guinea Pig ◽  
Mycobacterium Bovis ◽  
Host Response ◽  
Custom Made ◽  
Guinea Pig Model ◽  
Type Response

ABSTRACT Immune responses in the guinea pig model are understudied because of a lack of commercial reagents. We have developed a custom-made guinea pig oligonucleotide microarray (81 spots) and have examined the gene expression profile of splenocytes restimulated in vitro from Mycobacterium bovis BCG-vaccinated and naive animals. Eleven genes were significantly (P < 0.05) up-regulated following vaccination, indicating a Th1-type response. These results show that microarrays can be used to more fully define immune profiles of guinea pigs.

scholarly journals Identifying Bacterial and Host Factors Involved in the Interaction of Mycobacterium bovis with the Bovine Innate Immune Cells

2021 ◽  
Vol 12 ◽  
Author(s):  
Federico Carlos Blanco ◽  
María José Gravisaco ◽  
María Mercedes Bigi ◽  
Elizabeth Andrea García ◽  
Cecilia Marquez ◽  
...  
Keyword(s):  
Immune Response ◽  
Mycobacterium Bovis ◽  
Innate Immune Response ◽  
Mononuclear Cells ◽  
Immune Cell ◽  
Allelic Variation ◽  
Virulent Strain ◽  
Innate Immune ◽  
Peripheral Blood Mononuclear

Bovine tuberculosis is an important animal and zoonotic disease caused by Mycobacterium bovis. The innate immune response is the first line of defense against pathogens and is also crucial for the development of an efficient adaptive immune response. In this study we used an in vitro co-culture model of antigen presenting cells (APC) and autologous lymphocytes derived from peripheral blood mononuclear cells to identify the cell populations and immune mediators that participate in the development of an efficient innate response capable of controlling the intracellular replication of M. bovis. After M. bovis infection, bovine immune cell cultures displayed upregulated levels of iNOS, IL-22 and IFN-γ and the induction of the innate immune response was dependent on the presence of differentiated APC. Among the analyzed M. bovis isolates, only a live virulent M. bovis isolate induced an efficient innate immune response, which was increased upon stimulation of cell co-cultures with the M. bovis culture supernatant. Moreover, we demonstrated that an allelic variation of the early secreted protein ESAT-6 (ESAT6 T63A) expressed in the virulent strain is involved in this increased innate immune response. These results highlight the relevance of the compounds secreted by live M. bovis as well as the variability among the assessed M. bovis strains to induce an efficient innate immune response.

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