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Transcriptomic responses in the host during mosquito-transmitted and blood passaged Plasmodium chabaudi infections.

ABSTRACT: Plasmoidium chabuadi AS infections initiated by mosquito transmitted infections give rise to an attenuated blood-stage infection when compared to serially blood passaged parasites. Furthermore, Plasmoidium chabuadi CB infections have an increased virulence as compared with Plasmoidium chabuadi AS. We compared the immune response in the spleens induced by these two types of parasites and two types of infection routes in order to determine what may cause this attenuation. Spleens were taken at several timepoints during the blood-stage infection and RNA-seq analysis was performed.

ORGANISM(S): Mus musculus

PROVIDER: GSE178515 | GEO | 2024/06/12

REPOSITORIES: GEO

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Project description:Natural infection with Plasmodium parasites, the causative agents of malaria, occurs via mosquito vectors. However, most of our knowledge of the immune response to the blood stages of Plasmodium is from infections initiated by injection of serially blood-passaged infected red blood cells, resulting in an incomplete life cycle in the mammalian host. Vector transmission of the rodent malaria parasite, Plasmodium chabaudi chabaudi AS has been shown to give rise to a more attenuated blood-stage infection in C57Bl/6J mice, when compared to infections initiated with serially blood-passaged P. chabaudi-infected red blood cells. In mouse models, the host immune response induced by parasites derived from natural mosquito transmission is likely to more closely resemble the immune responses to Plasmodium infections in humans. It is therefore important to determine how the host response differs between the two types of infections. As the spleen is considered to be a major contributor to the protective host response to P. chabaudi, we carried out a comparative transcriptomic analysis of the splenic response to recently mosquito-transmitted and serially blood-passaged parasites in C57Bl/6J mice. The attenuated infection arising from recently mosquito-transmitted parasites is characterised by an earlier and stronger myeloid- and IFNγ-related response. Analyses of spleen lysates from the two infections similarly showed stronger or earlier inflammatory cytokine and chemokine production in the recently mosquito-transmitted blood-stage infections. Furthermore, tissue macrophages, including red pulp macrophages, and IFNγ-signalling in myeloid cells, are required for the early control of P. chabaudi recently mosquito-transmitted parasites, thus contributing to the attenuation of mosquito-transmitted infections. The molecules responsible for this early activation response to recently-transmitted blood-stage parasites in mice would be important to identify, as they may help to elucidate the nature of the initial interactions between blood-stage parasites and the host immune system in naturally transmitted malaria.

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Transcriptomic responses in the host during mosquito-transmitted and blood passaged Plasmodium chabaudi infections.

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