Expression of intra- and extracellular granzymes in patients with typhoid fever.
<h4>Background</h4> <p>Typhoid fever, caused by the intracellular pathogen Salmonella (S.) enterica serovar Typhi, remains a major cause of morbidity and mortality worldwide. Granzymes are serine proteases promoting cytotoxic lymphocytes mediated eradication of intracellular patho...
| Main Authors: | , , , , , , , , |
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| Drugi avtorji: | |
| Format: | Journal article |
| Jezik: | English |
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Public Library of Science
2017
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| _version_ | 1826298456237408256 |
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| author | de Jong, H Garcia-Laorden, M Hoogendijk, A Parry, C Maude, R Dondorp, A Faiz, M van der Poll, T Wiersinga, W |
| author2 | Marks, F |
| author_facet | Marks, F de Jong, H Garcia-Laorden, M Hoogendijk, A Parry, C Maude, R Dondorp, A Faiz, M van der Poll, T Wiersinga, W |
| author_sort | de Jong, H |
| collection | OXFORD |
| description | <h4>Background</h4> <p>Typhoid fever, caused by the intracellular pathogen Salmonella (S.) enterica serovar Typhi, remains a major cause of morbidity and mortality worldwide. Granzymes are serine proteases promoting cytotoxic lymphocytes mediated eradication of intracellular pathogens via the induction of cell death and which can also play a role in inflammation. We aimed to characterize the expression of extracellular and intracellular granzymes in patients with typhoid fever and whether the extracellular levels of granzyme correlated with IFN-γ release.</p> <h4>Methods and principal findings</h4> <p>We analyzed soluble protein levels of extracellular granzyme A and B in healthy volunteers and patients with confirmed S. Typhi infection on admission and day of discharge, and investigated whether this correlated with interferon (IFN)-γ release, a cytokine significantly expressed in typhoid fever. The intracellular expression of granzyme A, B and K in subsets of lymphocytic cells was determined using flow cytometry. Patients demonstrated a marked increase of extracellular granzyme A and B in acute phase plasma and a correlation of both granzymes with IFN-γ release. In patients, lower plasma levels of granzyme B, but not granzyme A, were found at day of discharge compared to admission, indicating an association of granzyme B with stage of disease. Peripheral blood mononuclear cells of typhoid fever patients had a higher percentage of lymphocytic cells expressing intracellular granzyme A and granzyme B, but not granzyme K, compared to controls.</p> <h4>Conclusion</h4> <p>The marked increase observed in extra- and intracellular levels of granzyme expression in patients with typhoid fever, and the correlation with stage of disease, suggests a role for granzymes in the host response to this disease.</p> |
| first_indexed | 2024-03-07T04:47:07Z |
| format | Journal article |
| id | oxford-uuid:d3a952db-e7f2-472c-b4e0-831402063f73 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T04:47:07Z |
| publishDate | 2017 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | oxford-uuid:d3a952db-e7f2-472c-b4e0-831402063f732022-03-27T08:13:01ZExpression of intra- and extracellular granzymes in patients with typhoid fever.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:d3a952db-e7f2-472c-b4e0-831402063f73EnglishSymplectic Elements at OxfordPublic Library of Science2017de Jong, HGarcia-Laorden, MHoogendijk, AParry, CMaude, RDondorp, AFaiz, Mvan der Poll, TWiersinga, WMarks, F <h4>Background</h4> <p>Typhoid fever, caused by the intracellular pathogen Salmonella (S.) enterica serovar Typhi, remains a major cause of morbidity and mortality worldwide. Granzymes are serine proteases promoting cytotoxic lymphocytes mediated eradication of intracellular pathogens via the induction of cell death and which can also play a role in inflammation. We aimed to characterize the expression of extracellular and intracellular granzymes in patients with typhoid fever and whether the extracellular levels of granzyme correlated with IFN-γ release.</p> <h4>Methods and principal findings</h4> <p>We analyzed soluble protein levels of extracellular granzyme A and B in healthy volunteers and patients with confirmed S. Typhi infection on admission and day of discharge, and investigated whether this correlated with interferon (IFN)-γ release, a cytokine significantly expressed in typhoid fever. The intracellular expression of granzyme A, B and K in subsets of lymphocytic cells was determined using flow cytometry. Patients demonstrated a marked increase of extracellular granzyme A and B in acute phase plasma and a correlation of both granzymes with IFN-γ release. In patients, lower plasma levels of granzyme B, but not granzyme A, were found at day of discharge compared to admission, indicating an association of granzyme B with stage of disease. Peripheral blood mononuclear cells of typhoid fever patients had a higher percentage of lymphocytic cells expressing intracellular granzyme A and granzyme B, but not granzyme K, compared to controls.</p> <h4>Conclusion</h4> <p>The marked increase observed in extra- and intracellular levels of granzyme expression in patients with typhoid fever, and the correlation with stage of disease, suggests a role for granzymes in the host response to this disease.</p> |
| spellingShingle | de Jong, H Garcia-Laorden, M Hoogendijk, A Parry, C Maude, R Dondorp, A Faiz, M van der Poll, T Wiersinga, W Expression of intra- and extracellular granzymes in patients with typhoid fever. |
| title | Expression of intra- and extracellular granzymes in patients with typhoid fever. |
| title_full | Expression of intra- and extracellular granzymes in patients with typhoid fever. |
| title_fullStr | Expression of intra- and extracellular granzymes in patients with typhoid fever. |
| title_full_unstemmed | Expression of intra- and extracellular granzymes in patients with typhoid fever. |
| title_short | Expression of intra- and extracellular granzymes in patients with typhoid fever. |
| title_sort | expression of intra and extracellular granzymes in patients with typhoid fever |
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