HVEM and CD160: Regulators of Immunopathology During Malaria Blood-Stage
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HVEM and CD160: Regulators of Immunopathology During Malaria Blood-Stage. / Muscate, Franziska; Stetter, Nadine; Schramm, Christoph; Schulze Zur Wiesch, Julian; Bosurgi, Lidia; Jacobs, Thomas.
In: FRONT IMMUNOL, Vol. 9, 2018, p. 2611.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - HVEM and CD160: Regulators of Immunopathology During Malaria Blood-Stage
AU - Muscate, Franziska
AU - Stetter, Nadine
AU - Schramm, Christoph
AU - Schulze Zur Wiesch, Julian
AU - Bosurgi, Lidia
AU - Jacobs, Thomas
PY - 2018
Y1 - 2018
N2 - CD8+ T cells are key players during infection with the malaria parasite Plasmodium berghei ANKA (PbA). While they cannot provide protection against blood-stage parasites, they can cause immunopathology, thus leading to the severe manifestation of cerebral malaria. Hence, the tight control of CD8+ T cell function is key in order to prevent fatal outcomes. One major mechanism to control CD8+ T cell activation, proliferation and effector function is the integration of co-inhibitory and co-stimulatory signals. In this study, we show that one such pathway, the HVEM-CD160 axis, significantly impacts CD8+ T cell regulation and thereby the incidence of cerebral malaria. Here, we show that the co-stimulatory molecule HVEM is indeed required to maintain CD8+ T effector populations during infection. Additionally, by generating a CD160-/- mouse line, we observe that the HVEM ligand CD160 counterbalances stimulatory signals in highly activated and cytotoxic CD8+ T effector cells, thereby restricting immunopathology. Importantly, CD160 is also induced on cytotoxic CD8+ T cells during acute Plasmodium falciparum malaria in humans. In conclusion, CD160 is specifically expressed on highly activated CD8+ T effector cells that are harmful during the blood-stage of malaria.
AB - CD8+ T cells are key players during infection with the malaria parasite Plasmodium berghei ANKA (PbA). While they cannot provide protection against blood-stage parasites, they can cause immunopathology, thus leading to the severe manifestation of cerebral malaria. Hence, the tight control of CD8+ T cell function is key in order to prevent fatal outcomes. One major mechanism to control CD8+ T cell activation, proliferation and effector function is the integration of co-inhibitory and co-stimulatory signals. In this study, we show that one such pathway, the HVEM-CD160 axis, significantly impacts CD8+ T cell regulation and thereby the incidence of cerebral malaria. Here, we show that the co-stimulatory molecule HVEM is indeed required to maintain CD8+ T effector populations during infection. Additionally, by generating a CD160-/- mouse line, we observe that the HVEM ligand CD160 counterbalances stimulatory signals in highly activated and cytotoxic CD8+ T effector cells, thereby restricting immunopathology. Importantly, CD160 is also induced on cytotoxic CD8+ T cells during acute Plasmodium falciparum malaria in humans. In conclusion, CD160 is specifically expressed on highly activated CD8+ T effector cells that are harmful during the blood-stage of malaria.
KW - Journal Article
U2 - 10.3389/fimmu.2018.02611
DO - 10.3389/fimmu.2018.02611
M3 - SCORING: Journal article
C2 - 30483269
VL - 9
SP - 2611
JO - FRONT IMMUNOL
JF - FRONT IMMUNOL
SN - 1664-3224
ER -