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Transient deficiency of dendritic cells results in lack of a merozoite surface protein 1-specific CD4 T cell response during peak Plasmodium chabaudi blood-stage infection.

ABSTRACT: Splenic dendritic cells are crucial for controlling the immune response to malaria by initiating a CD4 gamma interferon (IFN-?) response early in a blood-stage infection, which contributes to parasite clearance as well as to acute-stage immunopathology. CD8(-) CD11c(high) dendritic cells have been described previously to be important antigen-presenting cells for induction of these CD4 T cell responses in the spleens of Plasmodium chabaudi-infected mice. However, when isolated during the period of maximum parasitemia and shortly thereafter, the dendritic cells transiently lose their ability to stimulate T cells, recovering only as the parasitemia is controlled. This loss of a CD4 T cell response is also observed in vivo during this part of the infection. CD4 T cells from a T cell receptor-transgenic mouse recognizing a peptide of merozoite surface protein 1 (MSP1) injected into BALB/c mice during peak parasitemia proliferate poorly, and very few cells produce IFN-? and interleukin-2 (IL-2), compared with transgenic T cells injected earlier in the blood-stage infection. CD8(-) dendritic cells at day 10 can process and present peptides on major histocompatibility complex (MHC) class II with an efficiency similar to that of dendritic cells from earlier in infection. The failure of the day 10 dendritic cells to activate MSP1-specific CD4 T cells fully in vitro is associated with reduced expression of CD86 and lower production of IL-12 rather than with induction of inhibitory DC receptors or production of IL-10.

SUBMITTER: Sponaas AM

PROVIDER: S-EPMC3497445 | biostudies-other | 2012 Dec

REPOSITORIES: biostudies-other

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Transient deficiency of dendritic cells results in lack of a merozoite surface protein 1-specific CD4 T cell response during peak Plasmodium chabaudi blood-stage infection.

Sponaas Anne-Marit AM Belyaev Nikolai N Falck-Hansen Mika M Potocnik Alexandre A Langhorne Jean J

Infection and immunity 20120924 12

Splenic dendritic cells are crucial for controlling the immune response to malaria by initiating a CD4 gamma interferon (IFN-γ) response early in a blood-stage infection, which contributes to parasite clearance as well as to acute-stage immunopathology. CD8(-) CD11c(high) dendritic cells have been described previously to be important antigen-presenting cells for induction of these CD4 T cell responses in the spleens of Plasmodium chabaudi-infected mice. However, when isolated during the period o ...[more]

PMID: 23006847

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Project description:The pivotal role of spleen CD4(+) T cells in the development of both malaria pathogenesis and protective immunity makes necessary a profound comprehension of the mechanisms involved in their activation and regulation during Plasmodium infection. Herein, we examined in detail the behaviour of non-conventional and conventional splenic CD4(+) T cells during P. chabaudi malaria. We took advantage of the fact that a great proportion of CD4(+) T cells generated in CD1d(-/-) mice are I-A(b)-restricted (conventional cells), while their counterparts in I-A(b-/-) mice are restricted by CD1d and other class IB major histocompatibility complex (MHC) molecules (non-conventional cells). We found that conventional CD4(+) T cells are the main protagonists of the immune response to infection, which develops in two consecutive phases concomitant with acute and chronic parasitaemias. The early phase of the conventional CD4(+) T cell response is intense and short lasting, rapidly providing large amounts of proinflammatory cytokines and helping follicular and marginal zone B cells to secrete polyclonal immunoglobulin. Both TNF-? and IFN-? production depend mostly on conventional CD4(+) T cells. IFN-? is produced simultaneously by non-conventional and conventional CD4(+) T cells. The early phase of the response finishes after a week of infection, with the elimination of a large proportion of CD4(+) T cells, which then gives opportunity to the development of acquired immunity. Unexpectedly, the major contribution of CD1d-restricted CD4(+) T cells occurs at the beginning of the second phase of the response, but not earlier, helping both IFN-? and parasite-specific antibody production. We concluded that conventional CD4(+) T cells have a central role from the onset of P. chabaudi malaria, acting in parallel with non-conventional CD4(+) T cells as a link between innate and acquired immunity. This study contributes to the understanding of malaria immunology and opens a perspective for future studies designed to decipher the molecular mechanisms behind immune responses to Plasmodium infection.

Dataset Information

Transient deficiency of dendritic cells results in lack of a merozoite surface protein 1-specific CD4 T cell response during peak Plasmodium chabaudi blood-stage infection.

Publications

Transient deficiency of dendritic cells results in lack of a merozoite surface protein 1-specific CD4 T cell response during peak Plasmodium chabaudi blood-stage infection.

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