Fluctuations of Spleen Cytokine and Blood Lactate, Importance of Cellular Immunity in Host Defense Against Blood Stage Malaria Plasmodium yoelii
Our previous studies of protective immunity and pathology against blood stage malaria parasites have shown that not only CD4+ T cells, but also CD8+ T cells and macrophages, are important for host defense against blood stage malaria infection. Furthermore, we found that Plasmodium yoelii 17XNL (PyNL...
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Format: | Article |
Language: | English |
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Frontiers Media S.A.
2019-09-01
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Series: | Frontiers in Immunology |
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Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2019.02207/full |
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doaj-85a157178c1b455faba847ff371b2c9d |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Takashi Imai Takashi Imai Kazutomo Suzue Ha Ngo-Thanh Suguri Ono Wakako Orita Haruka Suzuki Chikako Shimokawa Chikako Shimokawa Alex Olia Alex Olia Seiji Obi Tomoyo Taniguchi Hidekazu Ishida Luc Van Kaer Shigeo Murata Keiji Tanaka Hajime Hisaeda |
spellingShingle |
Takashi Imai Takashi Imai Kazutomo Suzue Ha Ngo-Thanh Suguri Ono Wakako Orita Haruka Suzuki Chikako Shimokawa Chikako Shimokawa Alex Olia Alex Olia Seiji Obi Tomoyo Taniguchi Hidekazu Ishida Luc Van Kaer Shigeo Murata Keiji Tanaka Hajime Hisaeda Fluctuations of Spleen Cytokine and Blood Lactate, Importance of Cellular Immunity in Host Defense Against Blood Stage Malaria Plasmodium yoelii Frontiers in Immunology malaria T cell CD8 T cell CD4 T cell macrophage erythroblast |
author_facet |
Takashi Imai Takashi Imai Kazutomo Suzue Ha Ngo-Thanh Suguri Ono Wakako Orita Haruka Suzuki Chikako Shimokawa Chikako Shimokawa Alex Olia Alex Olia Seiji Obi Tomoyo Taniguchi Hidekazu Ishida Luc Van Kaer Shigeo Murata Keiji Tanaka Hajime Hisaeda |
author_sort |
Takashi Imai |
title |
Fluctuations of Spleen Cytokine and Blood Lactate, Importance of Cellular Immunity in Host Defense Against Blood Stage Malaria Plasmodium yoelii |
title_short |
Fluctuations of Spleen Cytokine and Blood Lactate, Importance of Cellular Immunity in Host Defense Against Blood Stage Malaria Plasmodium yoelii |
title_full |
Fluctuations of Spleen Cytokine and Blood Lactate, Importance of Cellular Immunity in Host Defense Against Blood Stage Malaria Plasmodium yoelii |
title_fullStr |
Fluctuations of Spleen Cytokine and Blood Lactate, Importance of Cellular Immunity in Host Defense Against Blood Stage Malaria Plasmodium yoelii |
title_full_unstemmed |
Fluctuations of Spleen Cytokine and Blood Lactate, Importance of Cellular Immunity in Host Defense Against Blood Stage Malaria Plasmodium yoelii |
title_sort |
fluctuations of spleen cytokine and blood lactate, importance of cellular immunity in host defense against blood stage malaria plasmodium yoelii |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2019-09-01 |
description |
Our previous studies of protective immunity and pathology against blood stage malaria parasites have shown that not only CD4+ T cells, but also CD8+ T cells and macrophages, are important for host defense against blood stage malaria infection. Furthermore, we found that Plasmodium yoelii 17XNL (PyNL) parasitizes erythroblasts, the red blood cell (RBC) precursor cells, which then express MHC class I molecules. In the present study, we analyzed spleen cytokine production. In CD8+ T cell-depleted mice, IL-10 production in early stage infection was increased over two-fold relative to infected control animals and IL-10+ CD3− cells were increased, whereas IFN-γ production in the late stage of infection was decreased. At day 16 after PyNL infection, CD8+ T cells produced more IFN-γ than CD4+ T cells. We evaluated the involvement of the immunoproteasome in induction of immune CD8+ T cells, and the role of Fas in protection against PyNL both of which are downstream of IFN-γ. In cell transfer experiments, at least the single molecules LMP7, LMP2, and PA28 are not essential for CD8+ T cell induction. The Fas mutant LPR mouse was weaker in resistance to PyNL infection than WT mice, and 20% of the animals died. LPR-derived parasitized erythroid cells exhibited less externalization of phosphatidylserine (PS), and phagocytosis by macrophages was impaired. Furthermore, we tried to identify the cause of death in malaria infection. Blood lactate concentration was increased in the CD8+ T cell-depleted PyNL-infected group at day 19 (around peak parasitemia) to similar levels as day 7 after infection with a lethal strain of Py. When we injected mice with lactate at day 4 and 6 of PyNL infection, all mice died at day 8 despite demonstrating low parasitemia, suggesting that hyperlactatemia is one of the causes of death in CD8+ T cell-depleted PyNL-infected mice. We conclude that CD8+ T cells might control cytokine production to some extent and regulate hyperparasitemia and hyperlactatemia in protection against blood stage malaria parasites. |
topic |
malaria T cell CD8 T cell CD4 T cell macrophage erythroblast |
url |
https://www.frontiersin.org/article/10.3389/fimmu.2019.02207/full |
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doaj-85a157178c1b455faba847ff371b2c9d2020-11-25T01:51:12ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-09-011010.3389/fimmu.2019.02207473305Fluctuations of Spleen Cytokine and Blood Lactate, Importance of Cellular Immunity in Host Defense Against Blood Stage Malaria Plasmodium yoeliiTakashi Imai0Takashi Imai1Kazutomo Suzue2Ha Ngo-Thanh3Suguri Ono4Wakako Orita5Haruka Suzuki6Chikako Shimokawa7Chikako Shimokawa8Alex Olia9Alex Olia10Seiji Obi11Tomoyo Taniguchi12Hidekazu Ishida13Luc Van Kaer14Shigeo Murata15Keiji Tanaka16Hajime Hisaeda17Department of Infectious Diseases and Host Defense, Gunma University Graduate School of Medicine, Maebashi, JapanDepartment of Parasitology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, JapanDepartment of Infectious Diseases and Host Defense, Gunma University Graduate School of Medicine, Maebashi, JapanDepartment of Infectious Diseases and Host Defense, Gunma University Graduate School of Medicine, Maebashi, JapanDepartment of Infectious Diseases and Host Defense, Gunma University Graduate School of Medicine, Maebashi, JapanDepartment of Infectious Diseases and Host Defense, Gunma University Graduate School of Medicine, Maebashi, JapanDepartment of Infectious Diseases and Host Defense, Gunma University Graduate School of Medicine, Maebashi, JapanDepartment of Infectious Diseases and Host Defense, Gunma University Graduate School of Medicine, Maebashi, JapanDepartment of Parasitology, National Institute of Infectious Diseases, Tokyo, JapanDepartment of Infectious Diseases and Host Defense, Gunma University Graduate School of Medicine, Maebashi, JapanDepartment of Parasitology, National Institute of Infectious Diseases, Tokyo, JapanDepartment of Infectious Diseases and Host Defense, Gunma University Graduate School of Medicine, Maebashi, JapanCenter for Medical Education, Graduate School of Medicine, Gunma University, Maebashi, JapanDepartment of Parasitology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, JapanDepartment of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, United StatesLaboratory of Protein Metabolism, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, JapanLaboratory of Protein Metabolism, Tokyo Metropolitan Institute of Medical Science, Tokyo, JapanDepartment of Parasitology, National Institute of Infectious Diseases, Tokyo, JapanOur previous studies of protective immunity and pathology against blood stage malaria parasites have shown that not only CD4+ T cells, but also CD8+ T cells and macrophages, are important for host defense against blood stage malaria infection. Furthermore, we found that Plasmodium yoelii 17XNL (PyNL) parasitizes erythroblasts, the red blood cell (RBC) precursor cells, which then express MHC class I molecules. In the present study, we analyzed spleen cytokine production. In CD8+ T cell-depleted mice, IL-10 production in early stage infection was increased over two-fold relative to infected control animals and IL-10+ CD3− cells were increased, whereas IFN-γ production in the late stage of infection was decreased. At day 16 after PyNL infection, CD8+ T cells produced more IFN-γ than CD4+ T cells. We evaluated the involvement of the immunoproteasome in induction of immune CD8+ T cells, and the role of Fas in protection against PyNL both of which are downstream of IFN-γ. In cell transfer experiments, at least the single molecules LMP7, LMP2, and PA28 are not essential for CD8+ T cell induction. The Fas mutant LPR mouse was weaker in resistance to PyNL infection than WT mice, and 20% of the animals died. LPR-derived parasitized erythroid cells exhibited less externalization of phosphatidylserine (PS), and phagocytosis by macrophages was impaired. Furthermore, we tried to identify the cause of death in malaria infection. Blood lactate concentration was increased in the CD8+ T cell-depleted PyNL-infected group at day 19 (around peak parasitemia) to similar levels as day 7 after infection with a lethal strain of Py. When we injected mice with lactate at day 4 and 6 of PyNL infection, all mice died at day 8 despite demonstrating low parasitemia, suggesting that hyperlactatemia is one of the causes of death in CD8+ T cell-depleted PyNL-infected mice. We conclude that CD8+ T cells might control cytokine production to some extent and regulate hyperparasitemia and hyperlactatemia in protection against blood stage malaria parasites.https://www.frontiersin.org/article/10.3389/fimmu.2019.02207/fullmalariaT cellCD8 T cellCD4 T cellmacrophageerythroblast |