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POSTER PRESENTATIONS Open Access Prevalence of a type-I interferon immune response against malaria liver stage infection Peter Liehl 1* , Miguel Prudêncio 1 , Céline Carret 2 , Maria M Mota 1 From Parasite to Prevention: Advances in the understanding of malaria Edinburgh, UK. 20-22 October 2010 Plasmodium sporozoites, transmitted to the mammalian host through a mosquito bite, travel to the liver, where they invade hepatocytes and develop into a form that is then able to infect red blood cells [1]. In spite of the importance of innate immunity in controlling microbial infections, very little is known about its role during the liver stage of malaria infection. To determine which type of innate immune response is triggered by Plasmodium berghei ANKA sporozoites during the liver stage of malaria we investigated tran- scriptome variations in this organ 40 hours after infec- tion. We identified 69 genes, mainly classical type-I interferon stimulated genes, whose expression was induced at least 2-fold in comparison to non-infected control mice. Strikingly, the expression of all induced genes was reduced in Plasmodium-infected mice lacking a functional type-I interferon receptor (IFNAR1). Furthermore, we observed a 2-3 fold increase of liver parasite load in IFNAR1-deficient mice compared to their wild-type counterparts. Conversely, infection of wild-type mice after pre-stimulation of the type-I inter- feron response led to a reduction in liver infection. Altogether, our data demonstrate for the first time that Plasmodium berghei sporozoites are able to induce a type-I interferon immune response in the liver and that this innate immune response contributes to the host resistance during the malaria liver stage. Future work will address how this immune response is acti- vated during a liver infection by Plasmodium and how it inhibits the infection. Author details 1 Unidade de Malaria, Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, 1649-028 Lisboa, Portugal. 2 Unidade de Parasitologia Molecular, Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, 1649-028 Lisboa, Portugal. Published: 20 October 2010 Reference 1. Prudêncio M, Rodriguez A, Mota MM: The silent path to thousands of merozoites: the Plasmodium liver stage. Nat Rev Microbiol 2006, 4:849-856. doi:10.1186/1475-2875-9-S2-P19 Cite this article as: Liehl et al.: Prevalence of a type-I interferon immune response against malaria liver stage infection. Malaria Journal 2010 9(Suppl 2):P19. Submit your next manuscript to BioMed Central and take full advantage of: Convenient online submission Thorough peer review No space constraints or color figure charges Immediate publication on acceptance Inclusion in PubMed, CAS, Scopus and Google Scholar Research which is freely available for redistribution Submit your manuscript at www.biomedcentral.com/submit 1 Unidade de Malaria, Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, 1649-028 Lisboa, Portugal Full list of author information is available at the end of the article Liehl et al. Malaria Journal 2010, 9(Suppl 2):P19 http://www.malariajournal.com/content/9/S2/P19 © 2010 Liehl et al; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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POSTER PRESENTATIONS Open Access

Prevalence of a type-I interferon immuneresponse against malaria liver stage infectionPeter Liehl1*, Miguel Prudêncio1, Céline Carret2, Maria M Mota1

From Parasite to Prevention: Advances in the understanding of malariaEdinburgh, UK. 20-22 October 2010

Plasmodium sporozoites, transmitted to the mammalianhost through a mosquito bite, travel to the liver, wherethey invade hepatocytes and develop into a form that isthen able to infect red blood cells [1]. In spite of theimportance of innate immunity in controlling microbialinfections, very little is known about its role during theliver stage of malaria infection.To determine which type of innate immune response

is triggered by Plasmodium berghei ANKA sporozoitesduring the liver stage of malaria we investigated tran-scriptome variations in this organ 40 hours after infec-tion. We identified 69 genes, mainly classical type-Iinterferon stimulated genes, whose expression wasinduced at least 2-fold in comparison to non-infectedcontrol mice. Strikingly, the expression of all inducedgenes was reduced in Plasmodium-infected mice lackinga functional type-I interferon receptor (IFNAR1).Furthermore, we observed a 2-3 fold increase of liverparasite load in IFNAR1-deficient mice compared totheir wild-type counterparts. Conversely, infection ofwild-type mice after pre-stimulation of the type-I inter-feron response led to a reduction in liver infection.Altogether, our data demonstrate for the first time

that Plasmodium berghei sporozoites are able to inducea type-I interferon immune response in the liver andthat this innate immune response contributes to thehost resistance during the malaria liver stage. Futurework will address how this immune response is acti-vated during a liver infection by Plasmodium and how itinhibits the infection.

Author details1Unidade de Malaria, Instituto de Medicina Molecular, Faculdade deMedicina da Universidade de Lisboa, 1649-028 Lisboa, Portugal. 2Unidade de

Parasitologia Molecular, Instituto de Medicina Molecular, Faculdade deMedicina da Universidade de Lisboa, 1649-028 Lisboa, Portugal.

Published: 20 October 2010

Reference1. Prudêncio M, Rodriguez A, Mota MM: The silent path to thousands of

merozoites: the Plasmodium liver stage. Nat Rev Microbiol 2006, 4:849-856.

doi:10.1186/1475-2875-9-S2-P19Cite this article as: Liehl et al.: Prevalence of a type-I interferon immuneresponse against malaria liver stage infection. Malaria Journal 20109(Suppl 2):P19.

Submit your next manuscript to BioMed Centraland take full advantage of:

• Convenient online submission

• Thorough peer review

• No space constraints or color figure charges

• Immediate publication on acceptance

• Inclusion in PubMed, CAS, Scopus and Google Scholar

• Research which is freely available for redistribution

Submit your manuscript at www.biomedcentral.com/submit

1Unidade de Malaria, Instituto de Medicina Molecular, Faculdade deMedicina da Universidade de Lisboa, 1649-028 Lisboa, PortugalFull list of author information is available at the end of the article

Liehl et al. Malaria Journal 2010, 9(Suppl 2):P19http://www.malariajournal.com/content/9/S2/P19

© 2010 Liehl et al; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative CommonsAttribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction inany medium, provided the original work is properly cited.