MIF Proteins from Two Nematodes Recognize Sera of Onchocerciasis Patients and Stimulate Peripheral Blood Mononuclear Cells to Release TNF-α and iL-10 Cytokines
Journal of Diseases and Medicinal Plants
Volume 2, Issue 2, April 2016, Pages: 8-13
Received: Mar. 31, 2016;
Accepted: Apr. 13, 2016;
Published: May 17, 2016
Views 3274 Downloads 130
Boursou Djafsia, Department of Biological Sciences, Faculty of Science, University of Ngaoundere, Ngaoundere, Cameroon
Dieudonne Ndjonka, Department of Biological Sciences, Faculty of Science, University of Ngaoundere, Ngaoundere, Cameroon
Irene Ajonina-Ekoti, Department of Molecular Physiology, University of Münster, Muenster, North Rhine-Westphalia, Germany
Onchocerciasis is a human filarial disease which leads to blindness in its ultimate phase. The immunopathology of the disease categorize patients into two types regarding the symptoms of the sickness: the hypo-reactive (generalized) and the hyper-reactive (sowda) types. In vitro, the humoral response by sera from the two categories of patient to recombinant proteins from the human parasitic nematodes: Onchocerca volvulus and Strongyloides ratti and the free-living nematode: Caenorhabditis elegans showed differences in strength and specificity. Immune recognition of antigens from O. volvulus (extract, Ovmif 1 and OvSOD) and C. elegans (mif proteins) were evaluated in a western blot and an indirect enzyme linked-immunosorbent assay (ELISA) using 36 human sera. The response was determined as optical density (OD) read at 450 nm and an index value of recognition calculated. The rate of induction of pro and anti-inflammatory cytokines by the same proteins was assessed on peripheral blood mononuclear cells (PBMC). Variable amounts of recombinant proteins were incubated with PBMC at 5% CO2 in RPMI 1640 medium supplemented with antibiotic, bovine serum albumin, HEPES. Generally, there was a stronger recongnition of O. volvulus antigens than C. elegans antigens. However, a comparison of the index values by ANOVA using Bonferroni post-test showed a significantly stronger recognition of O. volvulus antigens by sera from sowda patients than the recognition by sera from the generalized form when compared to C. elegans antigens. The sowda sera were shown therefore to be specific to O. volvulus antigens. The stimulation of PBMC by recombinant proteins from the two categories of nematode induced globally a higher anti-inflammatory (iL-10) cytokine release compared to the pro-inflammatory (TNFα) cytokine. Again, there was a notable higher release of iL-10 and TNF-α by proteins from the parasitic nematodes compared to the free living nematode. The humoral immune response to a cocktail of recombinant proteins from O. volvulus and the bovine parasite Onchocerca ochengi should be evaluated.
MIF Proteins from Two Nematodes Recognize Sera of Onchocerciasis Patients and Stimulate Peripheral Blood Mononuclear Cells to Release TNF-α and iL-10 Cytokines, Journal of Diseases and Medicinal Plants.
Vol. 2, No. 2,
2016, pp. 8-13.
Achukwi MD, Harnett W, Renz A., 2000. Onchocerca ochengi transmission dynamics and the correlation of O. ochengi microfilaria density in cattle with the transmission potential. Vet. Res. 31 (6): 11.
Basáñez M-G, Pion SDS, Churcher TS, Breitling LP, Little MP, Boussinesq M., 2006. River Blindness: A Success Story under Threat? PLoS Med. 3.
Turner JD, Tendongfor N, Esum M, Johnston KL, Langley RS, Ford L, Faragher B, Specht S, Mand S, Hoerauf A, Enyong P, Wanji S, Taylor MJ., 2010. Macrofilaricidal Activity after Doxycycline Only Treatment of Onchocerca volvulus in an Area of Loa loa Co-Endemicity: A Randomized Controlled Trial. PLoS Negl. Trop. Dis. 4, e660.
Tropical disease research (TDR). 2005. Onchocerciasis. Seventeenth program report: progress 2003-2004. 44-49, TDR/GEN/05.1.
Dafa’alla TH, Ghalib HW, Abdelmageed A, Williams JF., 1992. The profile of IgG and IgG subclasses of onchocerciasis patients. Clin. Exp. Immunol. 88: 258–263.
Hewitson JP, Grainger JR, Maizels RM., 2009. Helminth immunoregulation: the role of parasite secreted proteins in modulating host immunity. Mol. Biochem. Parasitol. 167: 1–11.
Maizels RM, Yazdanbakhsh M., 2003. Immune Regulation by helminth parasites: cellular and molecular mechanisms. Nat. Rev. Immunol. 3: 733–744.
Rahmah N, Khairul Anuar A, Tengku Ariff RH, Zurainee MN, Noor A’shikin A, Fadzillah A, Maimunah A, Ashraful Haq J., 1998. Use of antifilarial IgG4-ELISA to detect Brugia malayi infection in an endemic area of Malaysia. Trop. Med. Inter. Hlth. 3: 184–188.
Mpagi JL, Büttner DW, Tischendorf FW, Erttmann KD, Brattig NW., 2000. Humoral responses to a secretory Onchocerca volvulus protein: differences in the pattern of antibody isotypes to recombinant Ov20/OvS1 in generalized and hyperreactive onchocerciasis. Parasit. Immunol. 22: 455–460.
Ajonina-Ekoti I, Ndjonka D, Tanyi MK, Wilbertz M, Younis AE, Boursou D, Kurosinski MA, Eberle R, Lüersen K, Perbandt M, Breloer M, Brattig NW, Liebau E., 2012. Functional characterization and immune recognition of the extracellular superoxide dismutase from the human pathogenic parasite Onchocerca volvulus (OvEC-SOD). Acta Trop. 124: 15–26.
Brattig NW, Büttner DW, Hoerauf A., 2001. Neutrophil accumulation around Onchocerca worms and chemotaxis of neutrophils are dependent on Wolbachia endobacteria. Microbes Infect. 3: 439–446.
Ho O, Edeghere H, Galadima M, Odama LD and Engelbrecht F., 2013. Antibody responses to a recombinant Onchocerca volvulus antigen (Ov1.9) by onchocerciasis patients before and two months after ivermectin treatment. Res. J. Biotech. 2 (1): 8-12.
Djafsia B, Ndjonka D, Dikti JV, van Hoorn S, Manchang K, Brattig N, Liebau E., 2015. Immune recognition of excretory and secretory products of the filarial nematode Onchocerca ochengi in cattle and human sera. J. Helminthol. 1–9.
Chandrashekar R, Masood K, Alvarez RM, Ogunrinade AF, Lujan R, Richards FO, Weil GJ., 1991. Molecular cloning and characterization of recombinant parasite antigens for immunodiagnosis of onchocerciasis. J. Clin. Invest. 88: 1460–1466.
Schierack P, Lucius R, Sonnenburg B, Schilling K, Hartmann S., 2003. Parasite-Specific Immunomodulatory Functions of Filarial Cystatin. Infect. Immun. 71: 2422–2429.
Schönemeyer A, Lucius R, Sonnenburg B, Brattig N, Sabat R, Schilling K, Bradley J, Hartmann S., 2001. Modulation of Human T Cell Responses and Macrophage Functions by Onchocystatin, a Secreted Protein of the Filarial Nematode Onchocerca volvulus. J. Immunol. 167: 3207–3215.
Brattig NW., 2004. Pathogenesis and host responses in human onchocerciasis: impact of Onchocerca filariae and Wolbachia endobacteria. Microbes Infect. 6: 113–128.
Maizels RM, Pearce EJ, Artis D, Yazdanbakhsh M, Wynn TA., 2009. Regulation of pathogenesis and immunity in helminth infections. J. Exp. Med. 206: 2059–2066.
Zang X, Taylor P, Wang JM, Meyer DJ, Scott AL, Walkinshaw MD, Maizels RM., 2002. Homologues of Human Macrophage Migration Inhibitory Factor from a Parasitic Nematode gene cloning, protein activity, and crystal structure. J. Biol. Chem. 277: 44261–44267.
Cho MK, Ahn SC, Kim D-H, Yu HS., 2010. Parasite excretory–secretory proteins elicit TRIF dependent CXCL1 and IL-6 mediated allergic inflammation. Parasit. Immunol. 32: 354–360.