Plasmodium vivax parasites alter the balance of myeloid and plasmacytoid dendritic cells and the induction of regulatory T cells

Abstract

Immunity induced by Plasmodium vivax infections leads to memory T-cell recruitment and activation during subsequent infections. Here, we investigated the role of regulatory T cells (Treg) in coordination with the host immune response during P. vivax infection. Our results showed a significant increase in the percentage of FOXP31 Treg, IL-10-secreting Type I Treg (Tr1) and IL-10 levels in patients with acute P. vivax infection as compared with those found in either naïve or immune controls. The concurrent increase in the Treg population could also be reproduced in vitro using peripheral blood mononuclear cells from naïve controls stimulated with crude antigens extracted from P. vivax-infected red blood cells. Acute P. vivax infections were associated with a significant decrease in the numbers of DC, indicating a general immunosuppression during P. vivax infections. However, unlike P. falciparum infections, we found that the ratio of myeloid DC (MDC) to plasmacytoid DC (PDC) was significantly lower in acute P. vivax patients than that of naïve and immune controls. Moreover, the reduction in PDC may be partly responsible for the poor antibody responses during P. vivax infections. Taken together, these results suggest that P. vivax parasites interact with DC, which alters the MDC/PDC ratio that potentially leads to Treg activation and IL-10 release.Key words: Dendritic cell . IL-10 . Malaria . Plasmodium vivax . Regulatory T cell Eur. J. Immunol. 2008. 38: 2697-2705 DOI 10.1002 Immunity to infection 2697 IntroductionMalaria is a common tropical disease causing deaths among Plasmodium falciparum-infected children mainly in Sub-Saharan Africa [1]. P. falciparum causes malignant tertian malaria that accounts for most malaria-associated deaths, whereas P. vivax causes relapsing fever and the infection rarely becomes fatal. Although a better understanding of immunity is needed for the design of effective vaccines, immune regulation in the host during malaria infection is not fully understood, and few studies have been conducted in patients with P. vivax infections. Our recent study has shown that anti-P. vivax antibody levels were very low in immune individuals living in endemic area and in patients with acute P. vivax malaria. For the cell-mediated arm, an acute P. vivax infection was associated with the activation of memory T cells belonging to either a cytotoxic or helper phenotype [2]. Additionally, previous evidence [3,4] shows that immunization with pre-erythrocytic antigens can induce IFN-g release. This suggests that P. vivax can activate the immune system via the Th1 pathway. However, a possible suppressing mechanism arises from the activation of regulatory T cells (Treg) as has been shown in a murine malaria study [5]. Treg constitutively express CD25, which is the IL-2/a chain receptor [6]. Co-presentation of CD25 with forkhead box protein P3 (FOXP3) dictates the immune-suppressive role of Treg via the release of . Treg have been shown to alter the balance between myeloid dendritic cells (MDC) and plasmacytoi...

Strong Impact of CD4+Foxp3+ Regulatory T Cells and Limited Effect of T Cell-Derived IL-10 on Pathogen Clearance during Plasmodium yoelii Infection

“…Likewise, an increase in the number of CD4 + CD25 + Foxp3 + Tregs has been observed in the peripheral blood of humans infected with P. falciparum (7,8) or P. vivax (9), and is apparently associated with P. falciparum parasitemia (10). Similar results were obtained from murine malaria models using P. yoelii or P. berghei (11,12).…”

CD4+CD25+Foxp3+Regulatory T Cells, Dendritic Cells, and Circulating Cytokines in Uncomplicated Malaria: Do Different Parasite Species Elicit Similar Host Responses?

“…Circulating DCs are affected by malaria parasites in two ways. First, we describe that acute P. vivax and P. falciparum infections induced a significant increase in the proportion of DCs that were CD123 ϩ (although the absolute numbers of circulating DCs with this phenotype remained unchanged), with a consequent decrease in the myeloid/plasmacytoid DC ratio (22). These changes were proportional to parasite loads in single-species infections and may drive immune responses to the less inflammatory Th2-type pathway (39).…”

“…Most studies have examined P. falciparum infections acquired under conditions of very intense transmission that prevail in Africa (3,13,27,48,49,50), and although experimental malaria models have revealed various patterns of cell activation and cytokine production according to the infecting parasite species and load (29), it remains unclear how humans regulate their immune responses when exposed to different malaria species and various transmission levels. Changes in peripheral populations of Treg cells (4,22) and DCs (22) during acute P. vivax malaria were recently characterized in Brazil and Thailand, but no data are available for P. falciparum infections in comparable settings of low endemicity. Here we sought to characterize peripheral populations of Treg cells and DCs and to compare levels of circulating cytokines in uncomplicated malaria patients infected with either P. vivax, P. falciparum, or both species and in apparently healthy controls living in the same area of endemicity and exposed to relatively low levels of malaria transmission.…”

Age-related susceptibility and resistance to nonlethal Plasmodium yoelii infection in C57BL/6 mice

“…the splenic Dc compartment is a heterogeneous population with subsets of cells differing in functions and morphologies (shortman and liu 2002). th1 responses are mainly mediated by mDcs (liu 2001, Kuwana 2002, Jangpatarapongsa et al 2008) and thus we compared the numbers of mDcs and Dc maturation as measured by the expression of Dcs maturation markers, MHc ii and cD86, which are essential for induction of t cell responses (sher et al 2003, cervi et al 2004).…”