Author:
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-
1.
Tamura A, Ohashi N, Urakami H, Miyamura S , 1995. Classification of Rickettsia tsutsugamushi in a new genus, Orientia gen. nov., as Orientia tsutsugamushi comb. nov. Int J Syst Bacteriol 45: 589–591.
-
2.
Taylor AJ, Paris DH, Newton PN , 2015. A systematic review of mortality from untreated scrub typhus (Orientia tsutsugamushi). PLoS Negl Trop Dis 9: e0003971.
-
3.
Charles D. Ericsson MJ, Fournier PE, Raoult D, 2004. Rickettsioses and the international traveler. Clin Infect Dis 39: 1493–1499.
-
4.
Weitzel T, Dittrich S, Lopez J, Phuklia W, Martinez-Valdebenito C, Velasquez K, Blacksell SD, Paris DH, Abarca K , 2016. Endemic scrub typhus in South America. N Engl J Med 375: 954–961.
-
5.
Buzza MS, Bird PI , 2006. Extracellular granzymes: current perspectives. Biol Chem 387: 827–837.
-
6.
Bots M, Medema JP , 2006. Granzymes at a glance. J Cell Sci 119: 5011–5014.
-
7.
Wargnier A, Legrosmaida S, Bosselut R, Bourge JF, Lafaurie C, Ghysdael J, Sasportes M, Paul P , 1995. Identification of human granzyme-B promoter regulatory elements interacting with activated T-cell-specific proteins: implication of ikaros and cbf binding-sites in promoter activation. Proc Natl Acad Sci USA 92: 6930–6934.
-
8.
Mellor-Heineke S, Villanueva J, Jordan MB, Marsh R, Zhang K, Bleesing JJ, Filipovich AH, Risma KA , 2013. Elevated granzyme B in cytotoxic lymphocytes is a signature of immune activation in hemophagocytic lymphohistiocytosis. Front Immunol 4: 72.
-
9.
van Daalen KR, Reijneveld JF, Bovenschen N , 2020. Modulation of inflammation by extracellular granzyme A. Front Immunol 11: 931.
-
10.
De Fost M, Chierakul W, Pimda K, Dondorp AM, White NJ, Van der Poll T, 2005. Activation of cytotoxic lymphocytes in patients with scrub typhus. Am J Trop Med Hyg 72: 465–467.
-
11.
Lee YM, Kim DM, Lee SH, Jang MS, Neupane GP , 2011. Phylogenetic analysis of the 56 kDa protein genes of Orientia tsutsugamushi in southwest area of Korea. Am J Trop Med Hyg 84: 250–254.
-
12.
Hu ML, Liu JW, Wu KL, Lu SN, Chiou SS, Kuo CH, Chuah SK, Wang JH, Hu TH, Chiu KW , 2005. Abnormal liver function in scrub typhus. Am J Trop Med Hyg 73: 667–668.
-
13.
Basnyat B, Belbase RH, Zimmerman MD, Woods CW, Reller LB, Murdoch DR , 2006. Clinical features of scrub typhus. Clin Infect Dis 42: 1505–1506.
-
14.
Chung JH, Lim SC, Yun NR, Shin SH, Kim CM, Kim DM , 2012. Scrub typhus hepatitis confirmed by immunohistochemical staining. World J Gastroenterol 18: 5138–5141.
-
15.
Kim TS, Shin EC , 2019. The activation of bystander CD8+ T cells and their roles in viral infection. Exp Mol Med 51: 1–9.
-
16.
Hauptmann M, Kolbaum J, Lilla S, Wozniak D, Gharaibeh M, Fleischer B, Keller CA , 2016. Protective and pathogenic roles of CD8+ T lymphocytes in murine Orientia tsutsugamushi infection. PLoS Negl Trop Dis 10: e0004991.
-
17.
Zloza A , 2006. Evaluating the Role of CD4 (Dim) CD8 (Bright) T Cells in Viral Immunity. Chicago, IL: Rush University.
-
18.
Kim DM, Kim SW, Choi SH, Yun NR , 2010. Clinical and laboratory findings associated with severe scrub typhus. BMC Infect Dis 10: 108.
-
19.
Lauw FN, Simpson AJ, Hack CE, Prins JM, Wolbink AM, van Deventer SJ, Chaowagul W, White NJ, van der Poll T , 2000. Soluble granzymes are released during human endotoxemia and in patients with severe infection due to Gram-negative bacteria. J Infect Dis 182: 206–213.
-
20.
Kaminski L, Riehn M, Abel A, Steeg C, Yar DD, Addai-Mensah O, Aminkiah F, Owusu-Dabo E, Jacobs T, Mackroth MS , 2019. Cytotoxic T cell-derived granzyme B is increased in severe Plasmodium falciparum malaria. Front Immunol 10: 2917.
-
21.
Napoli AM, Fast LD, Gardiner F, Nevola M, Machan JT , 2012. Increased granzyme levels in cytotoxic T lymphocytes are associated with disease severity in emergency department patients with severe sepsis. Shock 37: 257–262.
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Elevated Extracellular Levels of Granzymes in Patients with Scrub Typhus
Joo-Hee Hwang
Joo-Hee Hwang
Department of Internal Medicine, Jeonbuk National University Medical School, Jeonju, Republic of Korea;
Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, Republic of Korea
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Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, Republic of Korea
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Jeong-Hwan Hwang
Jeong-Hwan Hwang
Department of Internal Medicine, Jeonbuk National University Medical School, Jeonju, Republic of Korea;
Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, Republic of Korea
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Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, Republic of Korea
Search for other papers by Jeong-Hwan Hwang in
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Chang-Seop Lee
Chang-Seop Lee
Department of Internal Medicine, Jeonbuk National University Medical School, Jeonju, Republic of Korea;
Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, Republic of Korea
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Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, Republic of Korea
Search for other papers by Chang-Seop Lee in
Current site
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PubMed
ABSTRACT.
Scrub typhus is an acute febrile disease caused by Orientia tsutsugamushi, which is transmitted through chigger mites. Delayed treatment results in various complications and, in severe cases, death. Granzymes are secreted by cytotoxic T lymphocytes or natural killer cells and are known to play an important role in controlling intracellular pathogens. To date, few studies have been done on granzymes in patients with scrub typhus. In this study, granzymes A and B showed a significant increase during the acute stage of scrub typhus compared with healthy control subjects, and decreased sharply after treatment. In addition, granzymes A and B were significantly high in the moderately elevated liver enzyme group. In conclusion, it appears that the host during the acute phase of scrub typhus increases cytotoxic T-cell activity to control infection.
Author Notes
Financial support: This work was supported by the Basic Science Research Programs (NRF-2015R1D1A1A01060251 and NRF-2018R1D1A3B07049557) of the National Research Foundation of Korea, which are funded by the Ministry of Education and Fund of Biomedical Research Institute, Jeonbuk National University Hospital.
Authors’ addresses: Joo-Hee Hwang, Jeong-Hwan Hwang, and Chang-Seop Lee, Department of Internal Medicine, Jeonbuk National University Medical School, Jeonju, 54896, Republic of Korea, and the Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, Republic of Korea, E-mails: zany78@naver.com, smilehwang77@hanmail.net, and lcsmd@chonbuk.ac.kr.
ProCite
RefWorks
Reference Manager
BibTeX
Zotero
EndNote
-
1.
Tamura A, Ohashi N, Urakami H, Miyamura S , 1995. Classification of Rickettsia tsutsugamushi in a new genus, Orientia gen. nov., as Orientia tsutsugamushi comb. nov. Int J Syst Bacteriol 45: 589–591.
-
2.
Taylor AJ, Paris DH, Newton PN , 2015. A systematic review of mortality from untreated scrub typhus (Orientia tsutsugamushi). PLoS Negl Trop Dis 9: e0003971.
-
3.
Charles D. Ericsson MJ, Fournier PE, Raoult D, 2004. Rickettsioses and the international traveler. Clin Infect Dis 39: 1493–1499.
-
4.
Weitzel T, Dittrich S, Lopez J, Phuklia W, Martinez-Valdebenito C, Velasquez K, Blacksell SD, Paris DH, Abarca K , 2016. Endemic scrub typhus in South America. N Engl J Med 375: 954–961.
-
5.
Buzza MS, Bird PI , 2006. Extracellular granzymes: current perspectives. Biol Chem 387: 827–837.
-
6.
Bots M, Medema JP , 2006. Granzymes at a glance. J Cell Sci 119: 5011–5014.
-
7.
Wargnier A, Legrosmaida S, Bosselut R, Bourge JF, Lafaurie C, Ghysdael J, Sasportes M, Paul P , 1995. Identification of human granzyme-B promoter regulatory elements interacting with activated T-cell-specific proteins: implication of ikaros and cbf binding-sites in promoter activation. Proc Natl Acad Sci USA 92: 6930–6934.
-
8.
Mellor-Heineke S, Villanueva J, Jordan MB, Marsh R, Zhang K, Bleesing JJ, Filipovich AH, Risma KA , 2013. Elevated granzyme B in cytotoxic lymphocytes is a signature of immune activation in hemophagocytic lymphohistiocytosis. Front Immunol 4: 72.
-
9.
van Daalen KR, Reijneveld JF, Bovenschen N , 2020. Modulation of inflammation by extracellular granzyme A. Front Immunol 11: 931.
-
10.
De Fost M, Chierakul W, Pimda K, Dondorp AM, White NJ, Van der Poll T, 2005. Activation of cytotoxic lymphocytes in patients with scrub typhus. Am J Trop Med Hyg 72: 465–467.
-
11.
Lee YM, Kim DM, Lee SH, Jang MS, Neupane GP , 2011. Phylogenetic analysis of the 56 kDa protein genes of Orientia tsutsugamushi in southwest area of Korea. Am J Trop Med Hyg 84: 250–254.
-
12.
Hu ML, Liu JW, Wu KL, Lu SN, Chiou SS, Kuo CH, Chuah SK, Wang JH, Hu TH, Chiu KW , 2005. Abnormal liver function in scrub typhus. Am J Trop Med Hyg 73: 667–668.
-
13.
Basnyat B, Belbase RH, Zimmerman MD, Woods CW, Reller LB, Murdoch DR , 2006. Clinical features of scrub typhus. Clin Infect Dis 42: 1505–1506.
-
14.
Chung JH, Lim SC, Yun NR, Shin SH, Kim CM, Kim DM , 2012. Scrub typhus hepatitis confirmed by immunohistochemical staining. World J Gastroenterol 18: 5138–5141.
-
15.
Kim TS, Shin EC , 2019. The activation of bystander CD8+ T cells and their roles in viral infection. Exp Mol Med 51: 1–9.
-
16.
Hauptmann M, Kolbaum J, Lilla S, Wozniak D, Gharaibeh M, Fleischer B, Keller CA , 2016. Protective and pathogenic roles of CD8+ T lymphocytes in murine Orientia tsutsugamushi infection. PLoS Negl Trop Dis 10: e0004991.
-
17.
Zloza A , 2006. Evaluating the Role of CD4 (Dim) CD8 (Bright) T Cells in Viral Immunity. Chicago, IL: Rush University.
-
18.
Kim DM, Kim SW, Choi SH, Yun NR , 2010. Clinical and laboratory findings associated with severe scrub typhus. BMC Infect Dis 10: 108.
-
19.
Lauw FN, Simpson AJ, Hack CE, Prins JM, Wolbink AM, van Deventer SJ, Chaowagul W, White NJ, van der Poll T , 2000. Soluble granzymes are released during human endotoxemia and in patients with severe infection due to Gram-negative bacteria. J Infect Dis 182: 206–213.
-
20.
Kaminski L, Riehn M, Abel A, Steeg C, Yar DD, Addai-Mensah O, Aminkiah F, Owusu-Dabo E, Jacobs T, Mackroth MS , 2019. Cytotoxic T cell-derived granzyme B is increased in severe Plasmodium falciparum malaria. Front Immunol 10: 2917.
-
21.
Napoli AM, Fast LD, Gardiner F, Nevola M, Machan JT , 2012. Increased granzyme levels in cytotoxic T lymphocytes are associated with disease severity in emergency department patients with severe sepsis. Shock 37: 257–262.
| Past two years | Past Year | Past 30 Days | |
|---|---|---|---|
| Abstract Views | 506 | 158 | 8 |
| Full Text Views | 96 | 19 | 1 |
| PDF Downloads | 87 | 13 | 0 |