CTLA-4 blockade differentially influences the outcome of non-lethal and lethal Plasmodium yoelii infections.

Abstract

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.

• Authors: Bernd Lepenies, Iris Gaworski, Susanne Tartz, Jean Langhorne, Bernhard Fleischer, Thomas Jacobs
• Journal: Microbes and infection (Microbes Infect) Vol. 9 Issue 6 Pg. 687-94 (May 2007) ISSN: 1286-4579 [Print] France
• PMID: 17398134 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Blocking
• Antibodies, Monoclonal
• Antigens, CD
• Antigens, Differentiation
• CTLA-4 Antigen
• Ctla4 protein, mouse
• Tumor Necrosis Factor-alpha
• Interferon-gamma

Topics

• Animals
• Antibodies, Blocking (immunology, pharmacology)
• Antibodies, Monoclonal (immunology, pharmacology)
• Antigens, CD (drug effects, immunology)
• Antigens, Differentiation (drug effects, immunology)
• CTLA-4 Antigen
• Inflammation (pathology)
• Interferon-gamma (blood)
• Lymphocyte Activation
• Malaria (immunology, pathology, virology)
• Mice
• Mice, Inbred BALB C
• Parasitemia
• Plasmodium yoelii (pathogenicity)
• T-Lymphocytes (immunology)
• Tumor Necrosis Factor-alpha (blood)
• Virulence