Changes in the levels of cytokines, chemokines and malaria-specific antibodies in response to Plasmodium falciparum infection in children living in sympatry in Mali

Abstract

Background The Fulani are known to be less susceptible to Plasmodium falciparum malaria as reflected by lower parasitaemia and fewer clinical symptoms than other sympatric ethnic groups. So far most studies in these groups have been performed on adults, which is why little is known about these responses in children. This study was designed to provide more information on this gap. Methods Circulating inflammatory factors and antibody levels in children from the Fulani and Dogon ethnic groups were measured. The inflammatory cytokines; interleukin (IL)-1beta, IL-6, IL-8, IL-10, IL-12p70, tumor necrosis factor (TNF) and the chemokines; regulated on activation normal T cell expressed and secreted (RANTES), monokine-induced by IFN-gamma (MIG), monocyte chemotactic protein (MCP)-1 and IFN-gamma-inducible protein (IP)-10 were measured by cytometric bead arrays. The levels of interferon (IFN)-alpha, IFN-gamma and malaria-specific antibodies; immunoglobulin (Ig) G, IgM and IgG subclasses (IgG1-IgG4) were measured by ELISA. Results The results revealed that the Fulani children had higher levels of all tested cytokines compared to the Dogon, in particular IFN-gamma, a cytokine known to be involved in parasite clearance. Out of all the tested chemokines, only MCP-1 was increased in the Fulani compared to the Dogon. When dividing the children into infected and uninfected individuals, infected Dogon had significantly lower levels of RANTES compared to their uninfected peers, and significantly higher levels of MIG and IP-10 as well as MCP-1, although the latter did not reach statistical significance. In contrast, such patterns were not seen in the infected Fulani children and their chemokine levels remained unchanged upon infection compared to uninfected counterparts. Furthermore, the Fulani also had higher titres of malaria-specific IgG and IgM as well as IgG1-3 subclasses compared to the Dogon. Conclusions Taken together, this study demonstrates, in accordance with previous work, that Fulani children mount a stronger inflammatory and antibody response against P. falciparum parasites compared to the Dogon and that these differences are evident already at an early age. The inflammatory responses in the Fulani were not influenced by an active infection which could explain why less clinical symptoms are seen in this group.

Serum Cytokines as Biomarkers of Early Trypanosoma cruzi infection by Congenital Exposure

“…Previous studies have shown that MIG has a parasiticidal effect on Leishmania mexicana promastigotes in vitro and that it induces small lesions in the plasma membrane of the parasite that can eventually lead it to death, but also that it is unable to generate immediate lysis (21). Previous studies have also shown increased MIG levels in the circulation of infants infected with malaria (22,23) and visceral leishmaniasis (24), supporting an important role for this chemokine in vivo. In addition, the levels of MCP-1, a monocyte chemotactic factor produced by macrophages and endothelial cells (25), were also high in the circulation of T. cruzi-infected infants.…”

Ethnic differences in susceptibility to malaria: What have we learned from immuno-epidemiological studies in West Africa?

“…Consistent with these findings, plasma levels of the proinflammatory cytokines IL-6, IL-8, IL-12, IFN-␣ and IFN-␥ were higher in the Fulani compared to the Dogon, irrespective of infectious status, suggesting that Fulani children mount a stronger inflammatory and antibody response against the P. falciparum parasite compared to the Dogon. Data showed that these differences were evident already at an early age (Bostrom et al, 2012).…”

Plasmodium coatneyi in Rhesus Macaques Replicates the Multisystemic Dysfunction of Severe Malaria in Humans

“…With the exception of IFN-␥, TIMP-1, and NAP-2, no significant differences from baseline values were found in samples obtained 7 days after reaching the maximum clinical scores. IFN-␥ is essential for protection in clinical malaria (77,78); in fact, early production of IFN-␥ is a critical factor in the differences in susceptibility to malaria reported among sympatric ethnic groups living in Mali (79,80). However, overproduction of IFN-␥ has also been associated with anemia, exemplified by bone marrow suppression, dyserythropoiesis, and erythrophagocytosis (81).…”