CTLA-4 blockade differentially influences the outcome of non-lethal and lethal Plasmodium yoelii infections.
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CTLA-4 blockade differentially influences the outcome of non-lethal and lethal Plasmodium yoelii infections. / Lepenies, Bernd; Gaworski, Iris; Tartz, Susanne; Langhorne, Jean; Fleischer, Bernhard; Jacobs, Thomas.
in: MICROBES INFECT, Jahrgang 9, Nr. 6, 6, 2007, S. 687-694.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - CTLA-4 blockade differentially influences the outcome of non-lethal and lethal Plasmodium yoelii infections.
AU - Lepenies, Bernd
AU - Gaworski, Iris
AU - Tartz, Susanne
AU - Langhorne, Jean
AU - Fleischer, Bernhard
AU - Jacobs, Thomas
PY - 2007
Y1 - 2007
N2 - An immune response against malaria has to be tightly controlled. The production of pro-inflammatory cytokines is required to control parasites but the same cytokines are also involved in severe malaria. We have shown that CTLA-4 expression during Plasmodium berghei malaria dampens the immune response. This strain provokes a pro-inflammatory immune response that is associated with the pathology of cerebral malaria. Accordingly a blockade of CTLA-4 during the blood-stage of P. berghei malaria leads to an exacerbation of disease. To analyze the effects of a CTLA-4 blockade in a malaria model which is not prone to immune pathology we employed P. yoelii infection. Blood-stage infection led to a rapid induction of CTLA-4 on T cells. Using the non-lethal P. yoelii strain Py17NL we found that a blockade of CTLA-4 resulted in an increased T cell activation and IFN-gamma production, which was accompanied by a lower peak parasitemia and earlier parasite clearance. In contrast, blockade of CTLA-4 during infection with a P. yoelii strain exhibiting a higher parasitemia induced markedly increased serum-levels of TNF-alpha, which was associated with severe inflammation and reduced survival.
AB - An immune response against malaria has to be tightly controlled. The production of pro-inflammatory cytokines is required to control parasites but the same cytokines are also involved in severe malaria. We have shown that CTLA-4 expression during Plasmodium berghei malaria dampens the immune response. This strain provokes a pro-inflammatory immune response that is associated with the pathology of cerebral malaria. Accordingly a blockade of CTLA-4 during the blood-stage of P. berghei malaria leads to an exacerbation of disease. To analyze the effects of a CTLA-4 blockade in a malaria model which is not prone to immune pathology we employed P. yoelii infection. Blood-stage infection led to a rapid induction of CTLA-4 on T cells. Using the non-lethal P. yoelii strain Py17NL we found that a blockade of CTLA-4 resulted in an increased T cell activation and IFN-gamma production, which was accompanied by a lower peak parasitemia and earlier parasite clearance. In contrast, blockade of CTLA-4 during infection with a P. yoelii strain exhibiting a higher parasitemia induced markedly increased serum-levels of TNF-alpha, which was associated with severe inflammation and reduced survival.
M3 - SCORING: Zeitschriftenaufsatz
VL - 9
SP - 687
EP - 694
JO - MICROBES INFECT
JF - MICROBES INFECT
SN - 1286-4579
IS - 6
M1 - 6
ER -
