scholarly journals Peripheral blood bovine lymphocytes and MAP show distinctly different proteome changes and immune pathways in host-pathogen interaction

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e8130 ◽  
Author(s):  
Kristina J.H. Kleinwort ◽  
Stefanie M. Hauck ◽  
Roxane L. Degroote ◽  
Armin M. Scholz ◽  
Christina Hölzel ◽  
...  

Mycobacterium avium subsp. paratuberculosis (MAP) is a pathogen causing paratuberculosis in cattle and small ruminants. During the long asymptomatic subclinical stage, high numbers of MAP are excreted and can be transmitted to food for human consumption, where they survive many of the standard techniques of food decontamination. Whether MAP is a human pathogen is currently under debate. The aim of this study was a better understanding of the host-pathogen response by analyzing the interaction of peripheral blood lymphocytes (PBL) from cattle with MAP in their exoproteomes/secretomes to gain more information about the pathogenic mechanisms of MAP. Because in other mycobacterial infections, the immune phenotype correlates with susceptibility, we additionally tested the interaction of MAP with recently detected cattle with a different immune capacity referred as immune deviant (ID) cows. In PBL, different biological pathways were enhanced in response to MAP dependent on the immune phenotype of the host. PBL of control cows activated members of cell activation and chemotaxis of leukocytes pathway as well as IL-12 mediated signaling. In contrast, in ID cows CNOT1 was detected as highly abundant protein, pointing to a different immune response, which could be favorable for MAP. Additionally, MAP exoproteomes differed in either GroEL1 or DnaK abundance, depending on the interacting host immune response. These finding point to an interdependent, tightly regulated response of the bovine immune system to MAP and vise versa.

2019 ◽  
Author(s):  
Kristina J.H. Kleinwort ◽  
Stefanie M. Hauck ◽  
Roxane L. Degroote ◽  
Armin M. Scholz ◽  
Christina Hölzel ◽  
...  

AbstractMycobacterium avium subsp. paratuberculosis (MAP) is a pathogen causing paratuberculosis in cattle and small ruminants. During the long asymptomatic subclinical stage, high numbers of MAP are excreted and can be transmitted to food, where they survive many of the standard techniques of food decontamination. If these MAP are harmful to the consumers is currently under debate. In general, there is a lack of information regarding interaction of the hosts immune system with MAP.In this study, we tested the interaction of peripheral blood lymphocytes (PBL) from cattle with MAP in their exoproteomes/secretomes. Because in other mycobacterial infections, the immune phenotype correlates with susceptibility, we additionally tested the interaction of MAP with recently detected immune deviant cows.In PBL, different biological pathways were enhanced in response to MAP dependent on the immune phenotype of the host. PBL of control cows activated members of cell activation and chemotaxis of leukocytes pathway as well as IL-12 mediated signaling. In contrast, in ID cows CNOT1 was detected as highly abundant protein, pointing to a different immune response, which could be favorable for MAP. Additionally, MAP reacted different to the hosts. Their exoproteomes differed in either GroEL1 or DnaK abundance, depending on the interacting immune response.These findings point to an interdependent, tightly regulated response of MAP and the immune system.


1982 ◽  
Vol 28 (9) ◽  
pp. 1887-1893 ◽  
Author(s):  
D F Ranney ◽  
A J Quattrone

Abstract Several common metabolites and drugs in the serum in of patients with inflammatory, infectious, autoimmune, immunodeficient, neoplastic, and toxicant-induced diseases can produce artifactual suppression of the [methyl-3H]-thymidine assay, which is widely used to evaluate lymphocyte responsiveness. We have developed a sensitive, semiautomated, fluorescence-enhancement assay in which true immunosuppressors are measured in the presence of absence of such interfering substances. Peripheral blood lymphocytes are activated with mitogens in standard microtiter culture trays. Changes in lymphocyte DNA content are quantified with a reagent formulation containing mithramycin, the fluorescence of which is enhanced on binding to DNA in the presence of MgCl2. We solubilize cells within the intact microtiter tray by using an automated, inverted "Array Sonicator," and measure fluorescence with an automated, photon-counting fluorometer. With this system, immune response modulation can be accurately assessed in the presence of patients' sera and other complex test substances (e.g., supernates from hybridomas, fermentation vats, viral preparations, and macrophage cultures.


2020 ◽  
Author(s):  
Anno Saris ◽  
Tom D.Y. Reijnders ◽  
Esther J. Nossent ◽  
Alex R. Schuurman ◽  
Jan Verhoeff ◽  
...  

AbstractOur understanding of the coronavirus disease-19 (COVID-19) immune response is almost exclusively derived from studies that examined blood. To gain insight in the pulmonary immune response we analysed BALF samples and paired blood samples from 17 severe COVID-19 patients. Macrophages and T cells were the most abundant cells in BALF. In the lungs, both CD4 and CD8 T cells were predominantly effector memory cells and expressed higher levels of the exhaustion marker PD-1 than in peripheral blood. Prolonged ICU stay associated with a reduced proportion of activated T cells in peripheral blood and even more so in BALF. T cell activation in blood, but not in BALF, was higher in fatal COVID-19 cases. Increased levels of inflammatory mediators were more pronounced in BALF than in plasma. In conclusion, the bronchoalveolar immune response in COVID-19 has a unique local profile that strongly differs from the immune profile in peripheral blood.SummaryThe bronchoalveolar immune response in severe COVID-19 strongly differs from the peripheral blood immune profile. Fatal COVID-19 associated with T cell activation blood, but not in BALF.


Science ◽  
1963 ◽  
Vol 142 (3596) ◽  
pp. 1185-1187 ◽  
Author(s):  
K. Hirschhorn ◽  
F. Bach ◽  
R. L. Kolodny ◽  
I. L. Firschein ◽  
N. Hashem

Blood ◽  
1997 ◽  
Vol 89 (12) ◽  
pp. 4652-4658 ◽  
Author(s):  
Thomas V. Tittle ◽  
Andrew D. Weinberg ◽  
Cara N. Steinkeler ◽  
Richard T. Maziarz

Abstract The OX-40 molecule is expressed on the surface of recently activated T lymphocytes. The presence of OX-40 on CD4+ T cells was analyzed in a rat haplo-identical (parental → F1) bone marrow transplant model of acute graft-versus-host disease (aGVHD). Increased numbers of activated CD4+ T cells that expressed the OX-40 antigen were detected in peripheral blood soon after transplantation before the earliest sign of disease. The peak of OX-40 expression occurred 12 days posttransplantation with a range of 18% to 36% of circulating T cells and remained 10-fold above background, never returning to baseline. A slight increase in OX-40 expression (range, 1% to 6%) was also detected on peripheral blood lymphocytes from control syngeneic F1 → F1 recipients. OX-40+ T cells were isolated from spleen, skin, lymph node, and liver tissue of rats undergoing aGVHD, but not in syngeneic transplants. OX-40+ T cells isolated from these tissues were of donor origin and were shown to be allo-reactive. These data raise the possibility of using the OX-40 antibody to detect and deplete selectively the T cells that cause aGVHD.


2020 ◽  
Author(s):  
Huijia Zhao ◽  
Ling Li ◽  
Qi-fa Ye

Abstract Background: Acute rejection (AR) is one of common and critical complications after kidney transplantation, which gives rise to an increasing of allograft loss and even death. However, the potential mechanisms of AR remain incompletely understood at present. This study aimed to reveal the underlying mechanisms and identify core biomarkers of AR.Methods: The AR gene expression profile GSE1563 involving 6 renal transplant patients undergoing AR and 9 patients with well-functioning transplant with no clinical evidence of rejection was selected to analyze the differentially expressed genes (DEGs) from purified RNA of peripheral blood lymphocytes. DAVID was used to carry out Gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. A protein-protein interaction (PPI) network was built to display the interactions among these DEGs. To get further reliable significant genes and mechanisms, gene set enrichment analysis (GSEA) was applied to evaluate the hub gene analyzing via PPI network.Results: A total of 347 DEGs were captured, including 301 upregulated genes and 46 downregulated genes. Go and KEGG pathway analysis showed the DEGs were particularly enriched in immune response, inflammatory response to antigenic stimulus, RNA transport and protein stabilization. The PPI network indicated 3 modules were also mainly involved in immune response and RNA transport. 18 hub genes were selected in PPI network, among which there were 6 core genes evaluated by DAVID. By the way of GSEA, Oxidative stress was another potential mechanism besides immunity and ncRNA transport. Conclusion: Our analysis uncovered the immune response including humoral and cellular immunity, ncRNA transport as well as oxidative stress was the major mechanisms of AR associated respectively with MAPK8, CCL5, HMGB1, NCBP2, XPO1 and APP, which could be novel noninvasive biomarkers in peripheral blood for early diagnosis and could be helpful to the treatment of AR.


2020 ◽  
Author(s):  
Huijia Zhao ◽  
Ling Li ◽  
Qifa Ye

Abstract Background: Acute rejection (AR) is one of common and critical complications after kidney transplantation, which gives rise to an increasing of allograft loss and even death. However, the potential mechanisms of AR remain incompletely understood at present. This study aimed to reveal the underlying mechanisms and identify core biomarkers of AR.Methods: The AR gene expression profile GSE1563 involving 6 renal transplant patients undergoing AR and 9 patients with well-functioning transplant with no clinical evidence of rejection was selected to analyze the differentially expressed genes (DEGs) from purified RNA of peripheral blood lymphocytes. DAVID was used to carry out Gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. A protein-protein interaction (PPI) network was built to display the interactions among these DEGs. To get further reliable significant genes and mechanisms, gene set enrichment analysis (GSEA) was applied to evaluate the hub gene analyzing via PPI network.Results: A total of 347 DEGs were captured, including 301 upregulated genes and 46 downregulated genes. Go and KEGG pathway analysis showed the DEGs were particularly enriched in immune response, inflammatory response to antigenic stimulus, RNA transport and protein stabilization. The PPI network indicated 3 modules were also mainly involved in immune response and RNA transport. 18 hub genes were selected in PPI network, among which there were 6 core genes evaluated by DAVID. By the way of GSEA, Oxidative stress was another potential mechanism besides immunity and ncRNA transport. Conclusion: Our analysis uncovered the immune response including humoral and cellular immunity, ncRNA transport as well as oxidative stress was the major mechanisms of AR associated respectively with MAPK8, CCL5, HMGB1, NCBP2, XPO1 and APP, which could be novel noninvasive biomarkers in peripheral blood for early diagnosis and could be helpful to the treatment of AR.


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