Plasma cytokines, chemokines and cellular immune responses in pre-school Nigerian children infected with Plasmodium falciparum

Abstract

BackgroundMalaria is a major cause of morbidity and mortality worldwide with over one million deaths annually, particularly in children under five years. This study was the first to examine plasma cytokines, chemokines and cellular immune responses in pre-school Nigerian children infected with Plasmodium falciparum from four semi-urban villages near Ile-Ife, Osun State, Nigeria.MethodsBlood was obtained from 231 children (aged 39–73 months) who were classified according to mean P. falciparum density per μl of blood (uninfected (n = 89), low density (<1,000, n = 51), medium density (1,000-10,000, n = 65) and high density (>10,000, n = 22)). IL-12p70, IL-10, Nitric oxide, IFN-γ, TNF, IL-17, IL-4 and TGF-β, C-C chemokine RANTES, MMP-8 and TIMP-1 were measured in plasma. Peripheral blood mononuclear cells were obtained and examined markers of innate immune cells (CD14, CD36, CD56, CD54, CD11c AND HLA-DR). T-cell sub-populations (CD4, CD3 and γδTCR) were intracellularly stained for IL-10, IFN-γ and TNF following polyclonal stimulation or stimulated with malaria parasites. Ascaris lumbricoides was endemic in these villages and all data were analysed taking into account the potential impact of bystander helminth infection. All data were analysed using SPSS 15 for windows and in all tests, p <0.05 was deemed significant.ResultsThe level of P. falciparum parasitaemia was positively associated with plasma IL-10 and negatively associated with IL-12p70. The percentage of monocytes was significantly decreased in malaria-infected individuals while malaria parasitaemia was positively associated with increasing percentages of CD54+, CD11c+ and CD56+ cell populations. No association was observed in cytokine expression in mitogen-activated T-cell populations between groups and no malaria specific immune responses were detected. Although A. lumbricoides is endemic in these villages, an analysis of the data showed no impact of this helminth infection on P. falciparum parasitaemia or on immune responses associated with P. falciparum infection.ConclusionsThese findings indicate that Nigerian children infected with P. falciparum exhibit immune responses associated with active malaria infection and these responses were positively associated with increased P. falciparum parasitaemia.

A novel in vitro model reveals distinctive modulatory roles of Plasmodium falciparum and Plasmodium vivax on naïve cell-mediated immunity

“…Signs of defective immune priming were also seen in this study, as shown by a decrease in the population of professional antigen presenting cells, dendritic cells, after exposure to P. falciparum while the number of these antigen presenting cells was similar to control cultures after exposure to P. vivax . In addition, the opposite effects of P. falciparum and P. vivax on the expression of HLA-DR in monocytes and dendritic cells described here supports previous findings reported by others [33]. Interestingly, the two types of antigen from P. falciparum increased expression of HLA-DR on the surface of monocytes which could be an incidence of severe outcome from immune over activation as reported in autoimmune disease patients [34].…”

NF90 regulation of immune factor expression in response to malaria antigens

“…Analysis of THP-1 cells treated with lysates of red blood cells infected or not with Plasmodium falciparum revealed that NF90 influenced the levels of immune response proteins in response to malaria antigens on different levels: transcription, mRNA turnover, and translation. In line with previous results [24], the number of CD14 + cells declined after treatment with lysates of red blood cells infected with P. falciparum, while NF90 silencing restored CD14 + cells. We propose that NF90 regulates gene expression programs in THP-1 cells and influences the ability of these cells to respond to malaria antigens.…”

“…These molecular changes were translated into changes in cellular responses. The reduction of CD14 + THP-1 cells treated with iRBC lysates, compared with uRBC lysates, mimicked the decline in circulating CD14 + monocytes observed previously in individuals infected with P. falciparum [24,35], as monocytes differentiate into macrophages and dendritic cells to respond to the infection. In this scenario, NF90 appears to contribute to reducing CD14 + cells, since silencing NF90 elevated the CD14 + pool.…”

Associations Between Helminth Infections, Plasmodium falciparum Parasite Carriage and Antibody Responses to Sexual and Asexual Stage Malarial Antigens

“…However, studies that have assessed this question have yielded conflicting results indicating that larger and better designed studies are needed. [17][18][19][20] To date, studies assessing the coinfection of helminths and malaria have mainly focused on the asexual forms of P. falciparum (reviewed in reference 21). However, there are indications that helminth infections may also influence the prevalence or density of P. falciparum gametocytes, the parasite stage responsible for transmission of infections to mosquitoes.…”