Pro-inflammatory Cytokine Response and Genetic Diversity in Merozoite Surface Protein 2 of Plasmodium falciparum Isolates from Nigeria

Authors
Olusola Ajibaye 1
Akinniyi A Osuntoki 2
Albert OT Ebuehi 2
Bamidele A Iwalokun 3
Emmanuel O Balogun 4
Kathleen N Egbuna 3
1 Biochemistry and Nutrition Division, Nigerian Institute of Medical Research; Department of Biochemistry, College of Medicine, University of Lagos, Lagos, Nigeria
2 Department of Biochemistry, College of Medicine, University of Lagos, Lagos, Nigeria
3 Biochemistry and Nutrition Division, Nigerian Institute of Medical Research, Lagos, Nigeria
4 Department of Biomedical Chemistry, Graduate School of Medicine, University of Tokyo, Tokyo 113-0033, Japan; Department of Biochemistry, Ahmadu Bello University, Zaria 2222, Nigeria
Abstract
Background: Polymorphisms in Plasmodium falciparum merozoite surface protein-2 (msp-2) and associated parasite genetic diversity which varies between malaria-endemic regions remain a limitation in malaria vaccine development. Pro-inflammatory cytokines are important in immunity against malaria, understanding the influence of genetic diversity on cytokine response is important for effective vaccine design. Methods: P. falciparum isolates obtained from 300 Nigerians with uncomplicated falciparum malaria at Ijede General Hospital, Ijede (IJE), General Hospital Ajeromi, Ajeromi (AJE) and Saint Kizito Mission Hospital, Lekki, were genotyped by nested polymerase chain reaction of msp-2 block 3 while ELISA was used to determine the pro-inflammatory cytokine response to describe the genetic diversity of P. falciparum. Results: Eighteen alleles were observed for msp-2 loci. Of the 195 isolates, 61 (31.0%) had only FC27-type alleles, 38 (19.7%) had only 3D7-type alleles, and 49.3% had multiple parasite lines with both alleles. Band sizes were 275–625 bp for FC27 and 150–425 bp for 3D7. Four alleles were observed from LEK, 2 (375–425 bp) and 2 (275–325 bp) of FC27-and 3D7-types, respectively; 12 alleles from AJE, 9 (275–625 bp) and 3 (325–425 bp) of FC27-types and 3D7-types, respectively; while IJE had a total of 12 alleles, 9 (275–625 bp) and 3 (325–425 bp) of FC27-types and 3D7-types, respectively. Mean multiplicity of infection (MOI) was 1.54. Heterozygosity (HE) ranged from 0.77 to 0.87 and was highest for IJE (0.87). Cytokine response was higher among <5 years and was significantly associated with MOI (P > 0.05) but with neither parasite density nor infection type. Conclusion: P. falciparum genetic diversity is extensive in Nigeria, protection via pro-inflammatory cytokines have little or no interplay with infection multiplicity

Keywords

1.
Baum J, Chen L, Healer J, Lopaticki S, Boyle M, Triglia T, et al. Reticulocyte-binding protein homologue 5 – An essential adhesin involved in invasion of human erythrocytes by Plasmodium falciparum. Int J Parasitol 2009;39:371-80.  Back to cited text no. 1
    
2.
Kyabayinze DJ, Karamagi C, Kiggundu M, Kamya MR, Wabwire-Mangen F, Kironde F, et al. Multiplicity of Plasmodium falciparum infection predicts antimalarial treatment outcome in Ugandan children. Afr Health Sci 2008;8:200-5.  Back to cited text no. 2
    
3.
Takala SL, Escalante AA, Branch OH, Kariuki S, Biswas S, Chaiyaroj SC, et al. Genetic diversity in the block 2 region of the merozoite surface protein 1 (MSP-1) of Plasmodium falciparum: Additional complexity and selection and convergence in fragment size polymorphism. Infect Genet Evol 2006;6:417-24.  Back to cited text no. 3
    
4.
Ferreira MU, Hartl DL. Plasmodium falciparum: Worldwide sequence diversity and evolution of the malaria vaccine candidate merozoite surface protein-2 (MSP-2). Exp Parasitol 2007;115:32-40.  Back to cited text no. 4
    
5.
Assefa SA, Preston MD, Campino S, Ocholla H, Sutherland CJ, Clark TG. estMOI: Estimating multiplicity of infection using parasite deep sequencing data. Bioinformatics 2014;30:1292-4.  Back to cited text no. 5
    
6.
Ibara-Okabande R, Koukouikila-Koussounda F, Ndounga M, Vouvoungui J, Malonga V, Casimiro PN, Ibara JR, Sidibe A, and Ntoumi F. Reduction of multiplicity of infections but no change in msp2 genetic diversity in Plasmodium falciparum isolates from Congolese children after introduction of artemisinin-combination therapy. Malar J 2012;11:410.  Back to cited text no. 6
    
7.
Aubouy A, Migot-Nabias F, Deloron P. Polymorphism in two merozoite surface proteins of Plasmodium falciparum isolates from Gabon. Malar J 2003;2:12.  Back to cited text no. 7
    
8.
Ntoumi F, Contamin H, Rogier C, Bonnefoy S, Trape JF, Mercereau-Puijalon O. Age-dependent carriage of multiple Plasmodium falciparum merozoite surface antigen-2 alleles in asymptomatic malaria infections. Am J Trop Med Hyg 1995;52:81-8.  Back to cited text no. 8
    
9.
Farouk SE, Dolo A, Bereczky S, Kouriba B, Maiga B, Farnet A, et al. Different antibody- and cytokine mediated responses to Plasmodium falciparum parasite in two sympatric ethnic tribes living in Mali. Microbes and Infection 2005;7:110-7.  Back to cited text no. 9
    
10.
Moncunill G, Mayor A, Jiménez A, Nhabomba A, Puyol L, Manaca MN, et al. Cytokine and antibody responses to Plasmodium falciparum in naïve individuals during a first malaria episode: Effect of age and malaria exposure. PLoS One 2013;8:e55756.  Back to cited text no. 10
    
11.
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;56:103-14.  Back to cited text no. 11
    
12.
Fillol F, Sarr JB, Boulanger D, Cisse B, Sokhna C, Riveau G, et al. Impact of child malnutrition on the specific anti-Plasmodium falciparum antibody response. Malar J 2009;8:116.  Back to cited text no. 12
    
13.
Zhang G, Manaca MN, McNamara-Smith M, Mayor A, Nhabomba A, Berthoud TK, et al. Interleukin-10 (IL-10) polymorphisms are associated with IL-10 production and clinical malaria in young children. Infect Immun 2012;80:2316-22.  Back to cited text no. 13
    
14.
Lyke KE, Burges R, Cissoko Y, Sangare L, Dao M, Diarra I, et al. 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;72:5630-7.  Back to cited text no. 14
    
15.
Borges QI, Fontes CJ, Damazo AS. Analysis of lymphocytes in patients with Plasmodium vivax malaria and its relation to the annexin-A1 and IL-10. Malar J 2013;12:455.  Back to cited text no. 15
    
16.
Mayengue PI, Ndounga M, Malonga FV, Bitemo M, Ntoumi F. Genetic polymorphism of merozoite surface protein-1 and merozoite surface protein-2 in Plasmodium falciparum isolates from Brazzaville, Republic of Congo. Malar J 2011;10:276.  Back to cited text no. 16
    
17.
Miller LH, Roberts T, Shahabuddin M, McCutchan TF. Analysis of sequence diversity in the Plasmodium falciparum merozoite surface protein-1 (MSP-1). Mol Biochem Parasitol 1993;59:1-14.  Back to cited text no. 17
    
18.
Oyedeji SI, Awobode HO, Kun J. Limited Genetic diversity and low multiplicity of Plasmodium falciparum infections in children with severe malaria in Lafia, North-central Nigeria. J Exp Clin Med 2013; 5: 143-147.  Back to cited text no. 18
    
19.
Kiwuwa MS, Ribacke U, Moll K, Byarugaba J, Lundblom K, Färnert A, et al. Genetic diversity of Plasmodium falciparum infections in mild and severe malaria of children from Kampala, Uganda. Parasitol Res 2013;112:1691-700.  Back to cited text no. 19
    
20.
Amodu OK, Olaniyan SA, Omotade OO. Changes in Plasmodium falciparum population dynamics in two populations at different time periods in Ibadan, South West Nigeria. Afr J Biomed Res 2015;18:17-22.  Back to cited text no. 20
    
21.
Ojurongbe O, Ogungbamigbe TO, Fagbenro-Beyioku AF, Fendel R, Kremsner PG, Kun JF. Rapid detection of Pfcrt and Pfmdr1 mutations in Plasmodium falciparum isolates by FRET andin vivo response to chloroquine among children from Osogbo, Nigeria. Malar J 2007;6:41.  Back to cited text no. 21
    
22.
Oyebola MK, Idowu ET, Olukosi YA, Iwalokun BA, Agomo CO, Ajibaye OO, et al. Genetic diversity and complexity of Plasmodium falciparum infections in Lagos, Nigeria. Asian Pac J Trop Biomed 2014;4 Suppl 1:S87-91.  Back to cited text no. 22
    
23.
Barry AE, Schultz L, Senn N, Nale J, Kiniboro B, Siba PM, et al. High levels of genetic diversity of Plasmodium falciparum populations in Papua New Guinea despite variable infection prevalence. Am J Trop Med Hyg 2013;88:718-25.  Back to cited text no. 23
    
24.
Mohammed H, Mindaye T, Belayneh M, Kassa M, Assefa A, Tadesse M,et al. Genetic diversity of Plasmodium falciparum isolates based on MSP-1 and MSP-2 genes from Kolla-Shele area, Arbaminch Zuria District, southwest Ethiopia. Malaria journal. 2015;1:1.  Back to cited text no. 24
    
25.
Hartl DL, Clark AG. Principles of Population Genetics. Sunderland, MD: Sinauer Associates; 1997.  Back to cited text no. 25
    
26.
Sanders PR, Gilson PR, Cantin GT, Greenbaum DC, Nebl T, Carucci DJ, et al. Distinct protein classes including novel merozoite surface antigens in raft-like membranes of Plasmodium falciparum. J Biol Chem 2005;280:40169-76.  Back to cited text no. 26
    
27.
al-Yaman F, Genton B, Anders R, Taraika J, Ginny M, Mellor S, et al. Assessment of the role of the humoral response to Plasmodium falciparum MSP2 compared to RESA and SPf66 in protecting Papua New Guinean children from clinical malaria. Parasite Immunol 1995;17:493-501.  Back to cited text no. 27
    
28.
Stanisic DI, Richards JS, McCallum FJ, Michon P, King CL, Schoepflin S, et al. Immunoglobulin G subclass-specific responses against Plasmodium falciparum merozoite antigens are associated with control of parasitemia and protection from symptomatic illness. Infect Immun 2009;77:1165-74.  Back to cited text no. 28
Advanced Biomedical Research
Volume 2017, November
November 2017
Pages 1-7