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Classical CD11c⁺ dendritic cells, not plasmacytoid dendritic cells, induce T cell responses to Plasmodium chabaudi malaria

Author:
Voisine, Cecile, Mastelic, Beatris, Sponaas, Anne-Marit, Langhorne, Jean
Source:
International journal for parasitology 2010 v.40 no.6 pp. 711-719
ISSN:
0020-7519
Subject:
CD4-positive T-lymphocytes, Plasmodium chabaudi, Toll-like receptor 9, dendritic cells, disease control, erythrocytes, immune response, immunopathology, major histocompatibility complex, malaria, mice, parasites
Abstract:
Dendritic cells play an important role in the development of immune responses in malaria, but the contribution of plasmacytoid dendritic cells (pDC) to CD4 T cell activation and immunopathology is unknown. We have investigated pDC in a Plasmodium chabaudi infection in mice. During infection, pDC increased in number and transiently up-regulated expression of Major Histocompatibility Complex class II and co-stimulatory molecules. However, in contrast to classical CD11chigh DC, pDC could not phagocytose parasites or process parasite proteins, to activate CD4 T cells. Activation of naïve pDC, but not CD11chigh DC, by infected red blood cells induced IFNα in vitro, which was dependent on the Toll-like receptor, TLR9. However, inactivation of TLR9 in knock-out mice had no effect on a P. chabaudi infection suggesting that TLR9 was not crucial for parasite elimination or pathology. Neither pDC nor IFNαβ were essential for parasite clearance as mice depleted of pDC or IFNαβ Receptor-knock-out mice could control infection. However, these mice lost significantly more weight than untreated or wild-type mice. We conclude that classical DC are the major antigen-presenting cells for CD4 T cells in this infection, but that pDC and IFNαβ may play minor roles in controlling the magnitude of acute stage pathology.
Agid:
2240600