Expression of intra- and extracellular granzymes in patients with typhoid fever.

Abstract

BACKGROUND:

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.

METHODS AND PRINCIPAL FINDINGS:

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.

CONCLUSION:

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.

• Authors: 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
• Journal: PLoS neglected tropical diseases (PLoS Negl Trop Dis) Vol. 11 Issue 7 Pg. e0005823 (Jul 2017) ISSN: 1935-2735 [Electronic] United States
• PMID: 28749963 (Publication Type: Journal Article)

Chemical References

• Interferon-gamma
• GZMB protein, human
• Granzymes
• GZMA protein, human

Topics

• Adult
• Bangladesh
• Case-Control Studies
• Female
• Flow Cytometry
• Granzymes (blood)
• Humans
• Interferon-gamma (blood)
• Killer Cells, Natural (immunology)
• Lymphocyte Count
• Male
• Middle Aged
• Prospective Studies
• Salmonella typhi (isolation & purification)
• T-Lymphocytes (immunology)
• Typhoid Fever (blood, diagnosis)
• Young Adult