Expression of intra- and extracellular granzymes in patients with typhoid fever.
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 w...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2017-07-01
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| Series: | PLoS Neglected Tropical Diseases |
| Online Access: | http://europepmc.org/articles/PMC5549753?pdf=render |
| _version_ | 1817980447900041216 |
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| author | Hanna K de Jong Maria Isabel Garcia-Laorden Arie J Hoogendijk Christopher M Parry Rapeephan R Maude Arjen M Dondorp Mohammed Abul Faiz Tom van der Poll Willem Joost Wiersinga |
| author_facet | Hanna K de Jong Maria Isabel Garcia-Laorden Arie J Hoogendijk Christopher M Parry Rapeephan R Maude Arjen M Dondorp Mohammed Abul Faiz Tom van der Poll Willem Joost Wiersinga |
| author_sort | Hanna K de Jong |
| collection | DOAJ |
| description | 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.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.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. |
| first_indexed | 2024-04-13T22:53:56Z |
| format | Article |
| id | doaj.art-5ef6b617943a479385f0c841baff6a18 |
| institution | Directory Open Access Journal |
| issn | 1935-2727 1935-2735 |
| language | English |
| last_indexed | 2024-04-13T22:53:56Z |
| publishDate | 2017-07-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Neglected Tropical Diseases |
| spelling | doaj.art-5ef6b617943a479385f0c841baff6a182022-12-22T02:26:05ZengPublic Library of Science (PLoS)PLoS Neglected Tropical Diseases1935-27271935-27352017-07-01117e000582310.1371/journal.pntd.0005823Expression of intra- and extracellular granzymes in patients with typhoid fever.Hanna K de JongMaria Isabel Garcia-LaordenArie J HoogendijkChristopher M ParryRapeephan R MaudeArjen M DondorpMohammed Abul FaizTom van der PollWillem Joost WiersingaTyphoid 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.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.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.http://europepmc.org/articles/PMC5549753?pdf=render |
| spellingShingle | Hanna K de Jong Maria Isabel Garcia-Laorden Arie J Hoogendijk Christopher M Parry Rapeephan R Maude Arjen M Dondorp Mohammed Abul Faiz Tom van der Poll Willem Joost Wiersinga Expression of intra- and extracellular granzymes in patients with typhoid fever. PLoS Neglected Tropical Diseases |
| 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 |
| url | http://europepmc.org/articles/PMC5549753?pdf=render |
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