The online version of this article (doi:10.1186/1475-2875-11-109) contains supplementary material, which is available to authorized users.
Pablo Giusti, Charles Arama contributed equally to this work.
The authors declare that they have no competing interests.
PG, CA, VD, BT, AD, OD and MTB conceived, designed and coordinated the study. PG and CA participated in the sample collection and processing. SB and MTB designed and supervised the immunoassays. SB carried out the immunoassays. SB and JP performed statistical analysis. SB drafted the first version of the manuscript. All authors read and approved the final manuscript.
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.
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.
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.
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.
Lyke KE, Burges R, Cissoko Y, Sangare L, Dao M, Diarra I, Kone A, Harley R, Plowe CV, Doumbo OK, Sztein MB: Serum levels of the proinflammatory cytokines interleukin-1 beta (IL-1beta), IL-6, IL-8, IL-10, tumor necrosis factor alpha, and IL-12(p70) in Malian children with severe Plasmodium falciparum malaria and matched uncomplicated malaria or healthy controls. Infect Immun. 2004, 72: 5630-5637. 10.1128/IAI.72.10.5630-5637.2004. PubMedCentralCrossRefPubMed
Wroczynska A, Nahorski W, Bakowska A, Pietkiewicz H: Cytokines and clinical manifestations of malaria in adults with severe and uncomplicated disease. Int Marit Health. 2005, 56: 103-114. PubMed
Jain V, Armah HB, Tongren JE, Ned RM, Wilson NO, Crawford S, Joel PK, Singh MP, Nagpal AC, Dash AP, Udhayakumar V, Singh N, Stiles JK: Plasma IP-10, apoptotic and angiogenic factors associated with fatal cerebral malaria in India. Malar J. 2008, 7: 83-10.1186/1475-2875-7-83. PubMedCentralCrossRefPubMed
Bolad A, Farouk SE, Israelsson E, Dolo A, Doumbo OK, Nebie I, Maiga B, Kouriba B, Luoni G, Sirima BS, Modiano D, Berzins K, Troye-Blomberg M: Distinct interethnic differences in immunoglobulin G class/subclass and immunoglobulin M antibody responses to malaria antigens but not in immunoglobulin G responses to nonmalarial antigens in sympatric tribes living in West Africa. Scand J Immunol. 2005, 61: 380-386. 10.1111/j.1365-3083.2005.01587.x. CrossRefPubMed
Israelsson E, Vafa M, Maiga B, Lysen A, Iriemenam NC, Dolo A, Doumbo OK, Troye-Blomberg M, Berzins K: Differences in Fcgamma receptor IIa genotypes and IgG subclass pattern of anti-malarial antibodies between sympatric ethnic groups in Mali. Malar J. 2008, 7: 175-10.1186/1475-2875-7-175. PubMedCentralCrossRefPubMed
Vafa M, Israelsson E, Maiga B, Dolo A, Doumbo OK, Troye-Blomberg M: Relationship between immunoglobulin isotype response to Plasmodium falciparum blood stage antigens and parasitological indexes as well as splenomegaly in sympatric ethnic groups living in Mali. Acta Trop. 2009, 109: 12-16. 10.1016/j.actatropica.2008.09.001. CrossRefPubMed
Dolo A, Modiano D, Maiga B, Daou M, Dolo G, Guindo H, Ba M, Maiga H, Coulibaly D, Perlman H, Blomberg MT, Toure YT, Coluzzi M, Doumbo O: Difference in susceptibility to malaria between two sympatric ethnic groups in Mali. AmJTrop Med Hyg. 2005, 72: 243-248.
Farouk SE, Dolo A, Bereczky S, Kouriba B, Maiga B, Farnert A, Perlmann H, Hayano M, Montgomery SM, Doumbo OK, Troye-Blomberg M: Different antibody- and cytokine-mediated responses to Plasmodium falciparum parasite in two sympatric ethnic tribes living in Mali. Microbes Infect. 2005, 7: 110-117. 10.1016/j.micinf.2004.09.012. CrossRefPubMed
Bereczky S, Dolo A, Maiga B, Hayano M, Granath F, Montgomery SM, Daou M, Arama C, Troye-Blomberg M, Doumbo OK, Farnert A: Spleen enlargement and genetic diversity of Plasmodium falciparum infection in two ethnic groups with different malaria susceptibility in Mali, West Africa. Trans R Soc Trop Med Hyg. 2006, 100: 248-257. 10.1016/j.trstmh.2005.03.011. CrossRefPubMed
Torcia MG, Santarlasci V, Cosmi L, Clemente A, Maggi L, Mangano VD, Verra F, Bancone G, Nebie I, Sirima BS, Liotta F, Frosali F, Angeli R, Severini C, Sannella AR, Bonini P, Lucibello M, Maggi E, Garaci E, Coluzzi M, Cozzolino F, Annunziato F, Romagnani S, Modiano D: Functional deficit of T regulatory cells in Fulani, an ethnic group with low susceptibility to Plasmodium falciparum malaria. Proc Natl Acad Sci USA. 2008, 105: 646-651. 10.1073/pnas.0709969105. PubMedCentralCrossRefPubMed
Modiano D, Luoni G, Sirima BS, Lanfrancotti A, Petrarca V, Cruciani F, Simpore J, Ciminelli BM, Foglietta E, Grisanti P, Bianco I, Modiano G, Coluzzi M: The lower susceptibility to Plasmodium falciparum malaria of Fulani of Burkina Faso (west Africa) is associated with low frequencies of classic malaria-resistance genes. Trans R Soc Trop Med Hyg. 2001, 95: 149-152. 10.1016/S0035-9203(01)90141-5. CrossRefPubMed
McCall MB, Hopman J, Daou M, Maiga B, Dara V, Ploemen I, Nganou-Makamdop K, Niangaly A, Tolo Y, Arama C, Bousema JT, van der Meer JW, van der Ven AJ, Troye-Blomberg M, Dolo A, Doumbo OK, Sauerwein RW: Early interferon-gamma response against Plasmodium falciparum correlates with interethnic differences in susceptibility to parasitemia between sympatric Fulani and Dogon in Mali. J Infect Dis. 2010, 201: 142-152. 10.1086/648596. CrossRefPubMed
Arama C, Giusti P, Bostrom S, Dara V, Traore B, Dolo A, Doumbo O, Varani S, Troye-Blomberg M: Interethnic differences in antigen-presenting cell activation and TLR responses in Malian children during Plasmodium falciparum malaria. PLoS One. 2011, 6: e18319-10.1371/journal.pone.0018319. PubMedCentralCrossRefPubMed
Jensen JB, Trager W: Plasmodium falciparum in culture: establishment of additional strains. AmJTrop Med Hyg. 1978, 27: 743-746.
Luty AJ, Lell B, Schmidt-Ott R, Lehman LG, Luckner D, Greve B, Matousek P, Herbich K, Schmid D, Migot-Nabias F, Deloron P, Nussenzweig RS, Kremsner PG: Interferon-gamma responses are associated with resistance to reinfection with Plasmodium falciparum in young African children. J Infect Dis. 1999, 179: 980-988. 10.1086/314689. CrossRefPubMed
Robinson LJ, D'Ombrain MC, Stanisic DI, Taraika J, Bernard N, Richards JS, Beeson JG, Tavul L, Michon P, Mueller I, Schofield L: Cellular tumor necrosis factor, gamma interferon, and interleukin-6 responses as correlates of immunity and risk of clinical Plasmodium falciparum malaria in children from Papua New Guinea. Infect Immun. 2009, 77: 3033-3043. 10.1128/IAI.00211-09. PubMedCentralCrossRefPubMed
Chaiyaroj SC, Rutta AS, Muenthaisong K, Watkins P, Na Ubol M, Looareesuwan S: Reduced levels of transforming growth factor-beta1, interleukin-12 and increased migration inhibitory factor are associated with severe malaria. Acta Trop. 2004, 89: 319-327. 10.1016/j.actatropica.2003.10.010. CrossRefPubMed
Were T, Hittner JB, Ouma C, Otieno RO, Orago AS, Ong'echa JM, Vulule JM, Keller CC, Perkins DJ: Suppression of RANTES in children with Plasmodium falciparum malaria. Haematologica. 2006, 91: 1396-1399. PubMed
Campanella GS, Tager AM, El Khoury JK, Thomas SY, Abrazinski TA, Manice LA, Colvin RA, Luster AD: Chemokine receptor CXCR3 and its ligands CXCL9 and CXCL10 are required for the development of murine cerebral malaria. Proc Natl Acad Sci USA. 2008, 105: 4814-4819. 10.1073/pnas.0801544105. PubMedCentralCrossRefPubMed
Hailu A, van der Poll T, Berhe N, Kager PA: Elevated plasma levels of interferon (IFN)-gamma, IFN-gamma inducing cytokines, and IFN-gamma inducible CXC chemokines in visceral leishmaniasis. AmJTrop Med Hyg. 2004, 71: 561-567.
Crompton PD, Kayala MA, Traore B, Kayentao K, Ongoiba A, Weiss GE, Molina DM, Burk CR, Waisberg M, Jasinskas A, Tan X, Doumbo S, Doumtabe D, Kone Y, Narum DL, Liang X, Doumbo OK, Miller LH, Doolan DL, Baldi P, Felgner PL, Pierce SK: A prospective analysis of the Ab response to Plasmodium falciparum before and after a malaria season by protein microarray. Proc Natl Acad Sci USA. 2010, 107: 6958-6963. 10.1073/pnas.1001323107. PubMedCentralCrossRefPubMed
- Changes in the levels of cytokines, chemokines and malaria-specific antibodies in response to Plasmodium falciparum infection in children living in sympatry in Mali
- BioMed Central
Neu im Fachgebiet Innere Medizin
Meistgelesene Bücher aus der Inneren Medizin
e.Med Kampagnen-Visual, Mail Icon II