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Adult Brugia malayi mitochondrial and nuclear fractions impart Th1-associated sizeable protection against infective larval challenges in Mastomys coucha

Published online by Cambridge University Press:  01 March 2009

S. Shakya ,
A.K. Srivastava  and
S. Misra-Bhattacharya
S. Shakya
Affiliation:
Divisions of Parasitology, Central Drug Research Institute, M.G. Marg, Post Box 173, Lucknow226001, Uttar Pradesh, India
A.K. Srivastava
Affiliation:
Divisions of Biochemistry, Central Drug Research Institute, M.G. Marg, Post Box 173, Lucknow226001, Uttar Pradesh, India
S. Misra-Bhattacharya*
Affiliation:
Divisions of Parasitology, Central Drug Research Institute, M.G. Marg, Post Box 173, Lucknow226001, Uttar Pradesh, India
*
*Fax: +91 0522 2623938/2623405 E-mail: shailja_cdri@rediffmail.com/shailjacdri@yahoo.com
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Abstract

Protective immunity to the subperiodic human filariid, Brugia malayi, was explored in the rodent host, Mastomys coucha after vaccination with subcellular fractions derived from the adult stage of the parasite. The highest level of protection was conferred in animals vaccinated with the ‘mitochondria rich’ (MT) fraction, in which microfilaraemia and worm burden were markedly reduced by 67.2 and 65.9%, respectively, followed by the ‘nucleus rich’ (NR) fraction, showing reductions of 62 and 52.3%, respectively, over the non-immunized control group. Mastomys vaccinated with MT and NR, displayed a significant increase in the level of antigen-specific serum immunoglobulin G (IgG). The levels of IgG2a, IgG2b and IgM antibody isotypes were remarkably elevated in both the MT and NR immunized groups, while IgG1 and IgG3 levels were low. Apart from antibodies, both these fractions also led to marked antigen-specific lymphoproliferation in vitro, along with enhanced release of nitric oxide by peritoneal macrophages. There was an increased population of CD4+ and CD8a+T-cells in MT immunized animals, as measured by flow cytometry, accompanied by elevated levels of proinflammatory cytokines; interferon gamma (IFN-γ), tumour necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β) in the culture supernatants of the activated splenocytes. The results suggest that both NR and MT contain proinflammatory molecules which evoke a protective Th1 type of immune response.

Type
Research Papers
Information
Journal of Helminthology , Volume 83 , Issue 1 , March 2009 , pp. 83 - 95
Copyright
Copyright © Cambridge University Press 2009

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References

Abdel Rahman, E.H., Abouel Ezz, N.M. & Abdel Megeed, K.N. (2005) Trichinella spiralis: affinity purified antigen based diagnosis and immunoprophylaxis. Journal of Egyptian Society of Parasitology 35, 379–393.Google ScholarPubMed
Ash, L.R. & Riley, J.M. (1970) Development of subperiodic Brugia malayi in the jird (Meriones unguiculatus) with notes on infection in other rodents. Journal of Parasitology 56, 969–972.CrossRefGoogle ScholarPubMed
Babayan, S.A., Attout, T., Harris, A., Taylor, M.D., Le Goff, L., Vuong, P.N., Rénia, L., Allen, J.E. & Bain, O. (2006) Vaccination against filarial nematodes with irradiated larvae provides long-term protection against the third larval stage but not against subsequent life cycle stages. International Journal of Parasitology 36, 903–914.CrossRefGoogle Scholar
Babu, S. & Nutman, T.B. (2003) Proinflammatory cytokines dominate the early immune response to filarial parasites. Journal of Immunology 171, 6723–6732.CrossRefGoogle ScholarPubMed
Babu, S., Shultz, L.D., Klei, T.R. & Rajan, T.V. (1999) Immunity in experimental murine filariasis: roles of T and B cells revisited. Infection and Immunity 67, 3166–3167.CrossRefGoogle Scholar
Babu, S., Blauvelt, C.P. & Nutman, T.B. (2007) Filarial parasites induce NK cell activation, type 1 and type 2 cytokine secretion, and subsequent apoptotic cell death. Journal of Immunology 179, 2445–2456.CrossRefGoogle ScholarPubMed
Bancroft, A. & Devaney, E. (1993) The analysis of the humoral response of the BALB/c mouse immunized with radiation attenuated third stage larvae of Brugia pahangi. Parasite Immunology 15, 153–162.CrossRefGoogle ScholarPubMed
Benthony, J.M., Loukas, A., Hotez, P.J. & Knox, D.P. (2006) Vaccines against blood feeding nematodes of human and live-stock. Parasitology 133, S63–S79.CrossRefGoogle Scholar
Blackwell, N.M. & Else, K.J. (2001) B cells and antibodies are required for resistance to the parasitic gastrointestinal nematode Trichuris muris. Infection and Immunity 69, 3860–3868.CrossRefGoogle Scholar
Blasco, J.M., Gamazo, C., Winter, A.J., Jiménez de Bagüés, M.P., Marín, C., Barberán, M., Moriyón, I., Alonso-Urmeneta, B. & Díaz, R. (1993) Evaluation of whole cell and subcellular vaccines against Brucella ovis in rams. Veterinary Immunology and Immunopathology 37, 257–270.CrossRefGoogle ScholarPubMed
Bleiss, W., Oberländer, U., Hartmann, S., Adam, R., Marko, A., Schönemeyer, A. & Lucius, R. (2002) Protective immunity induced by irradiated third-stage larvae of the filaria Acanthocheilonema viteae is directed against challenge third-stage larvae before molting. Journal of Parasitology 88, 264–270.CrossRefGoogle ScholarPubMed
Bourguinat, C., Pion, S.D.S., Kamgno, J., Gardon, J., Duke, B.O.L., Boussinesq, M. & Prichard, R.K. (2007) Genetic selection of low fertile Onchocerca volvulus by ivermectin treatment. PLoS Neglected Tropical Diseases 1, e72.CrossRefGoogle ScholarPubMed
Bradford, M.M. (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein dye binding. Analytical Biochemistry 72, 248–254.CrossRefGoogle ScholarPubMed
Bungiro, R.D. Jr, Sun, T., Harrison, L.M., Shoemaker, C.B. & Cappello, M. (2008) Mucosal antibody responses in experimental hookworm infection. Parasite Immunology 30, 293–303.CrossRefGoogle ScholarPubMed
Campbell, W.C. (1991) Ivermectin as an antiparasitic agent for use in humans. Annual Review of Microbiology 45, 445–474.CrossRefGoogle ScholarPubMed
Chatterjee, R.K., Singh, D.P. & Misra, S. (1992) Acanthocheilonema viteae in Mastomys natalensis: evaluation of efficacy of microfilarial vaccine. Current Science 63, 98–102.Google Scholar
Cumberbatch, M., Griffiths, C.E., Tucker, S.C., Dearman, R.J. & Kimber, I. (1999) Tumour necrosis factor-α induces Langerhans' cell migration in humans. British Journal of Dermatology 141, 192–197.CrossRefGoogle ScholarPubMed
De Duve, C. & Beaufay, H.A. (1981) A short history of tissue fractionation. Journal of Cell Biology 91, 293s–299s.CrossRefGoogle Scholar
Devaney, E. & Osborne, J. (2000) The third-stage larva (L3) of Brugia: its role in immune modulation and protective immunity. Microbes and Infection 2, 1363–1372.CrossRefGoogle ScholarPubMed
Dikshit, M. & Misra, S. (1994) Identification of protective molecules in excretory secretory products of the rodent filariid Acanthocheilonema viteae. Indian Journal of Parasitology 18, 45–52.Google Scholar
Dimock, K.A., Eberhard, M.L. & Lammie, P.J. (1996) Th1-like antifilarial immune responses predominate in antigen-negative persons. Infection Immunity 64, 2952–2967.CrossRefGoogle ScholarPubMed
Dixit, S., Gaur, R.L., Sahoo, M.K., Joseph, S.K., Murthy, P.S.R. & Murthy, P.K. (2006) Protection against L3 induced Brugia malayi infection in Mastomys coucha pre-immunized with BmAFII fraction of the filarial adult worm. Vaccine 24, 5824–5831.CrossRefGoogle ScholarPubMed
Elson, L.H., Calvopina, M., Paredes, W., Araujo, E., Bradley, J.E., Guderian, R.H. & Nutman, T.B. (1995) Immunity to onchocerciasis: putative immune individuals produce a Th1-like response to Onchocerca volvulus. Journal of Infectious Diseases 171, 652–658.CrossRefGoogle ScholarPubMed
Ferreira, C.C., Santoro, M.M. & Goes, A.M. (1998) Protective immunity induced in mice by F8.1 and F8.2 antigens purified from Schistosoma mansoni eggs. Memórias do Instituto Oswaldo Cruz 93, S185–S189.CrossRefGoogle ScholarPubMed
Flohe, S.B., Bauer, C., Flohe, S. & Moll, H. (1998) Antigen-pulsed epidermal Langerhans' cells protect susceptible mice from infection with the intracellular parasite Leishmania major. European Journal of Immunology 28, 3800–3821.3.0.CO;2-0>CrossRefGoogle ScholarPubMed
Fry, M. & Jenkins, D.C. (1983) Nippostrongylus brasiliensis and Ascaridia galli: mitochondrial respiration in free living and parasitic stages. Experimental Parasitology 56, 101–106.CrossRefGoogle ScholarPubMed
Goff, L., Martin, C., Oswald, I.P., Vuong, P.N., Petit, G., Ungeheuer, M.N. & Bain, O. (2000) Parasitology and immunology of mice vaccinated with irradiated Litosomoides sigmodontis larvae. Parasitology 120, 271–280.CrossRefGoogle Scholar
Green, L.C., Wagner, D.A., Glogowski, J., Skipper, P.L., Wishnok, J.S. & Tannenbaum, S.A. (1982) Analysis of nitrate, nitrite and [15N] nitrate in biological fluids. Analytical Biochemistry 126, 131–134.CrossRefGoogle ScholarPubMed
Gupta, R., Bajpai, P., Tripathi, L.M., Srivastava, V.M., Jain, S.K. & Misra-Bhattacharya, S. (2004) Macrophages in the development of protective immunity against experimental Brugia malayi infection. Parasitology 129, 311–323.CrossRefGoogle ScholarPubMed
Herbert, D.R., Nolan, T.J., Schad, G.A. & Abraham, D. (2002) The role of B cells in immunity against larval Strongyloides stercoralis in mice. Parasite Immunology 24, 95–101.CrossRefGoogle ScholarPubMed
Hotez, P.J., Zhan, B., Bethony, J.M., Loukas, A., Williamson, A., Goud, G.N., Hawdon, J.M., Dobardzic, A., Dobardzic, R., Ghosh, K., Bottazzi, M.E., Mendez, S., Zook, B., Wang, Y., Liu, S., Essiet-Gibson, I., Chung-Debose, S., Xiao, S.H., Knox, D., Meagher, M., Inan, M., Correa-Oliveira, R., Vilk, P., Shepherd, H.R., Brandt, W. & Russell, P.K. (2003) Progress in the development of a recombinant vaccine for human hookworm disease: the human hookworm vaccine initiative. International Journal for Parasitology 33, 1245–1258.CrossRefGoogle ScholarPubMed
Hunter, J.C. & Korzick, D.H. (2005) Protein kinase C distribution and translocation in rat myocardium: methodological considerations. Journal of Pharmacological and Toxicological Methods 51, 129–138.CrossRefGoogle ScholarPubMed
Hussain, R., Grogl, M. & Ottesen, A. (1987) Differential subclass recognition of parasite antigens correlates with different clinical manifestations of infection. Journal of Immunology 139, 2794–2798.CrossRefGoogle ScholarPubMed
Ismail, M.M., Jayakody, R.L., Weil, G.J., Fernando, D., de Silva, M.S., de Silva, G.A. & Balasooriya, W.K. (2001) Long-term efficacy of single-dose combinations of albendazole, ivermectin and diethylcarbamazine for the treatment of bancroftian filariasis. Transactions of the Royal Society of Tropical Medicine and Hygiene 95, 332–335.CrossRefGoogle ScholarPubMed
Kazura, J.W., Cicirello, H.C. & McCall, J.W. (1986) Induction of protection against Brugia malayi infection in jirds by microfilarial antigens. Journal of Immunology 136, 1422.CrossRefGoogle ScholarPubMed
King, C.L. (2001) Transmission intensity and human immune responses to lymphatic filariasis. Parasite Immunology 23, 363–371.CrossRefGoogle ScholarPubMed
Lustigman, S. & McCarter, J.P. (2007) Ivermectin resistance in Onchocerca volvulus: toward a genetic basis. PLoS Neglected Tropical Diseases 1, e76.CrossRefGoogle Scholar
Lustigman, S., MacDonald, A.J. & Abraham, D. (2003) CD4+-dependent immunity to Onchocerca volvulus third-stage larvae in humans and the mouse vaccination model: common ground and distinctions. International Journal for Parasitology 33, 1161–1171.CrossRefGoogle ScholarPubMed
Maizels, R.M. & Yazdanbakhsh, M. (2003) Immune regulation by helminth parasites: cellular and molecular mechanisms. Nature Reviews of Immunology 9, 733–744.CrossRefGoogle Scholar
Martin, C., Saeftel, M., Vuong, P.N., Babayan, S., Fischer, K., Bain, O. & Hoerauf, A. (2001) B-cell deficiency suppresses vaccine-induced protection against murine filariasis but does not increase the recovery rate for primary infection. Infection and Immunity 69, 7067–7073.CrossRefGoogle Scholar
McCall, J.W., Malove, J.B., Ah, H. & Thompson, P.E. (1973) Mongolian jirds (Meriones unguiculatus) infected with Brugia malayi by the intraperitoneal route. A rich source of developing larvae, adult filariae and microfilariae. Journal of Parasitology 59, 436–441.CrossRefGoogle Scholar
Melrose, W.D. & Rahmah, N. (2006) Use of Brugia rapid dipstick and ICT test to map distribution of lymphatic filariasis in the Democratic Republic of Timor-Leste. Southeast Asian Journal of Tropical Medicine and Public Health 37, 22–25.Google ScholarPubMed
Michael, E. & Bundy, D. (1997) Global mapping of lymphatic filariasis. Parasitology Today 13, 472–476.CrossRefGoogle ScholarPubMed
Misra, S., Mukherjee, M., Dikshit, M. & Chatterjee, R.K. (1998) Cellular immune response of gerbils and mastomys in experimental filariasis. Tropical Medicine and International Health 3, 124–129.CrossRefGoogle ScholarPubMed
Misra-Bhattacharya, S., Katiyar, D., Bajpai, P., Tripathi, R.P. & Saxena, J.K. (2004) 4-Methyl-7-(tetradecanoyl)-2H-1-benzopyran-2-one: a novel DNA topoisomerase II inhibitor with adulticidal and embryo static activity against sub periodic Brugia malayi. Parasitology Research 92, 177–182.CrossRefGoogle Scholar
Oothuman, P., Denham, D.A., McGreevy, P.B., Nelson, G.S. & Rogers, R. (1979) Successful vaccination of cats against Brugia pahangi with larvae attenuated by irradiation with 10 krad cobalt 60. Parasite Immunology 1, 209–216.CrossRefGoogle ScholarPubMed
Oswald, I.P., Wynn, T.A., Sher, A. & James, S.L. (1994) NO as an effector molecule of parasite killing: modulation of its synthesis by cytokines. Comparative Biochemistry Physiology Pharmacology Toxicology Endocrinology 108, 11–18.CrossRefGoogle ScholarPubMed
Ottesen, E.A. (2006) Lymphatic filariasis: treatment, control and elimination. Advances in Parasitology 61, 395–441.CrossRefGoogle ScholarPubMed
Ottesen, E.A. & Ramachandran, C.D. (1995) Lymphatic filariasis. Infection and disease: control strategies. Parasitology Today 11, 129–131.CrossRefGoogle Scholar
Ottesen, E.A., Duke, B.O., Karam, M. & Behbehani, K. (1997) Strategies and tools for the control/elimination of lymphatic filariasis. Bulletin of World Health Organization 75, 491–503.Google ScholarPubMed
Parker, C.D., Field, L.H., Berry, L.J. & Manclark, C. (1978) Subcellular fractions for immunizing against pertussis. Developing Biological Standards 41, 23–29.Google ScholarPubMed
Pearlman, E., Kroeze, W.K., Hazlett, F.E. Jr, Chen, S.S., Mawhorter, S.D., Boom, W.H. & Kazura, J.W. (1993) Brugia malayi: acquired resistance to microfilariae in BALB/c mice correlates with local Th2 responses. Experimental Parasitology 76, 200–208.CrossRefGoogle ScholarPubMed
Pfaff, A.W., Schulz-Key, H., Soboslay, P.T., Geiger, S.M. & Hoffmann, W.H. (2000) The role of nitric oxide in the innate resistance to microfilariae of Litosomoides sigmodontis in mice. Parasite Immunology 22, 397–405.CrossRefGoogle Scholar
Pokharel, D.R., Rai, R., Nandakumar Kodumudi, K., Reddy, M.V. & Rathaur, S. (2006) Vaccination with Setaria cervi 175 kDa collagenase induces high level of protection against Brugia malayi infection in jirds. Vaccine 24, 6208–6215.CrossRefGoogle ScholarPubMed
Pulendran, B., Smith, J.L., Caspary, G., Brasel, K., Pettit, D., Maraskovsky, E. & Maliszewski, C.R. (1999) Distinct dendritic cell subsets differentially regulate the class of immune response in vivo. Proceedings of National Academy of Science USA 96, 1036–1041.CrossRefGoogle ScholarPubMed
Rajan, B., Ramalingam, T. & Rajan, T.V. (2005) Critical role for IgM in host protection in experimental filarial infection. Journal of Immunology 175, 1827–1833.CrossRefGoogle ScholarPubMed
Rajan, T.V., Porte, P., Yates, J.A., Keefer, L. & Shultz, L.D. (1996) Role of nitric oxide in host defense against an extracellular, metazoan parasite, Brugia malayi. Infection and Immunity 64, 3351–3353.CrossRefGoogle ScholarPubMed
Ravindran, B. (2001) Are inflammation and immunological hyperactivity needed for filarial parasite development? Trends in Parasitology 17, 70–73.CrossRefGoogle ScholarPubMed
Rizzo, L.V., DeKruff, R.H. & Umetsu, D.T. (1992) Generation of B cell memory and affinity maturation: induction with Th1 and Th2 cell clones. Journal of Immunology 148, 3733–3739.CrossRefGoogle Scholar
Ruiz, A.M., Esteva, M., Cabeza Meckert, P., Laguens, R.P. & Segura, E.L. (1985) Protective immunity and pathology induced by inoculation of mice with different subcellular fractions of Trypanosoma cruzi. Acta Tropica 42, 299–309.Google ScholarPubMed
Saeftel, M., Volkmann, L., Korten, S., Brattig, N., Al-Qaoud, K., Fleischer, B. & Hoerauf, A. (2001) Lack of interferon-gamma confers impaired neutrophil granulocyte function and imparts prolonged survival of adult filarial worms in murine filariasis. Microbes and Infection 3, 203–213.CrossRefGoogle ScholarPubMed
Sato, H. & Kamiya, H. (1995) Role of epidermal Langerhans' cells in the induction of protective immunity to Schistosoma mansoni in guinea-pigs. Immunology 84, 233–238.Google ScholarPubMed
Schallig, H.D. & Van Leeuwen, M.A. (1997) Protective immunity to the blood-feeding nematode Haemonchus contortus induced by vaccination with parasite low molecular weight antigens. Parasitology 114, 293–299.CrossRefGoogle Scholar
Schroter, C.J., Braun, M., Englert, J., Beck, H., Schmid, H. & Kalbacher, H. (1999) A rapid method to separate endosomes from lysosomal contents using differential centrifugation and hypotonic lysis of lysosomes. Journal of Immunological Methods 227, 161–168.CrossRefGoogle ScholarPubMed
Semnani, R.T., Law, M., Kubofcik, J. & Nutman, T.B. (2004) Filaria-induced immune evasion: suppression by the infective stage of Brugia malayi at the earliest host-parasite interface. Journal of Immunology 172, 6229–6238.CrossRefGoogle ScholarPubMed
Singh, U., Misra, S., Murthy, P.K., Katiyar, J.C., Agarwal, A. & Sircar, A.R. (1997) Immunoreactive molecules of Brugia malayi and their diagnostic potential. Serodiagnosis and Immunotherapy of Infectious Diseases 8, 207–212.CrossRefGoogle Scholar
Spencer, L., Shultz, L. & Rajan, T.V. (2003) T cells are required for host protection against Brugia malayi but need not produce or respond to interleukin-4. Infection and Immunity 71, 3097–3106.CrossRefGoogle ScholarPubMed
Storey, D.M. & Mettias, E.F. (1980) Suppression of microfilaraemia in Litomosoides carinii infections in cotton rats by vaccination with adult worm homogenate. Annals of Tropical Medicine and Parasitology 74, 211–218.CrossRefGoogle ScholarPubMed
Sumati, , Saxena, R.P., Tandon, A., Saxena, K.C., Singh, D.P., Misra, S. & Chatterjee, R.K. (1990) Immunoprophylaxis against filarial parasite, Dipetalonema viteae in multimammate rat Mastomys natalensis: immunization with adult worm antigens. Indian Journal of Experimental Biology 28, 582–584.Google ScholarPubMed
Taubert, A. & Zahner, H. (2001) Cellular immune responses of filaria (Litosomoides sigmodontis) infected BALB/c mice detected on the level of cytokine transcription. Parasite Immunology 23, 453–462.CrossRefGoogle Scholar
Taylor, M., Cross, H., Mohammed, A., Trees, J. & Bianco, A.E. (1996) Susceptibility of Brugia malayi and Onchocerca lienalis microfilariae to nitric oxide and hydrogen peroxide in cell-free culture and from IFNγ-activated macrophages. Parasitology 112, 315–322.CrossRefGoogle Scholar
Thomas, R., McCrossan, M. & Selkirk, M. (1997) Cytostatic and cytotoxic effects of activated macrophages and nitric oxide donors on Brugia malayi. Infection and Immunity 65, 2732–2739.CrossRefGoogle ScholarPubMed
Wang, Z.Q., Cui, J., Wei, H.Y., Han, H.M., Zhang, H.W. & Li, Y.L. (2006) Vaccination of mice with DNA vaccine induces the immune response and partial protection against T. spiralis infection. Vaccine 24, 1205–1212.CrossRefGoogle ScholarPubMed
Weil, G.J., Li, B.W., Liftis, F. & Chandrashekar, R. (1992) Brugia malayi: antibody responses to larval antigens in infected and immunized jirds. Experimental Parasitology 74, 315–323.CrossRefGoogle ScholarPubMed