Abstract
Neurocysticercosis, caused by Taenia solium, is one of the most common causes of seizures worldwide. The symptoms result from granulomatous inflammation associated with dying cyst forms of the parasite. Although the invasive larvae can be killed by immune serum plus complement, immunity to the cyst stage depends on a cellular response. This dichotomous immune response is reminiscent of the extremes of the immune response associated with T helper 1 (Th1) and Th2 cytokine profiles. To characterize the cytokine response in cysticercosis, granulomas were removed from the peritoneal cavity of mice infected with Taenia crassiceps cysts and examined for cytokine message by in situ hybridization using 35S-labeled RNA probes. The granulomas were staged based on histologic appearance of the degenerating parasite. Message for gamma interferon (IFN-gamma) was identified by light microscopy in 11 of the 12 granulomas, and interleukin-2 (IL-2) message was identified in 9 of the 12. By laser scanning confocal microscopy, significantly increased IFN-gamma and IL-2 pixel intensity was identified in nearly all of the granulomas from early histologic stages. Message for IL-4 was seen in 6 of the 12 granulomas. Only granulomas with complete destruction of the parasite architecture displayed more than minimal amounts of IL-4 message by light microscopy, and only 2 of 12 granulomas had IL-4 pixel intensity significantly above background. Only minimal amounts of IL-10 message were detected in 4 of 11 granulomas. Thus, early granulomas in cysticercosis are predominantly associated with a Th1 response, whereas later granulomas, in which parasite destruction is complete, have a mixture of Th1 and IL-4. The Th1 response appears to play an important role both in the pathogenesis of disease as well as in the clearing of the parasites, with IL-4 involved in downregulation of the initial response.
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- Abraham K. M., Teale J. M. Isotype restriction during infection of mice with the cestode Mesocestoides corti: role of immune suppression. J Immunol. 1987 Mar 15;138(6):1699–1704. [PubMed] [Google Scholar]
- Bøgh H. O., Lightowlers M. W., Sullivan N. D., Mitchell G. F., Rickard M. D. Stage-specific immunity to Taenia taeniaeformis infection in mice. A histological study of the course of infection in mice vaccinated with either oncosphere or metacestode antigens. Parasite Immunol. 1990 Mar;12(2):153–162. doi: 10.1111/j.1365-3024.1990.tb00944.x. [DOI] [PubMed] [Google Scholar]
- Damian R. T. The exploitation of host immune responses by parasites. J Parasitol. 1987 Feb;73(1):3–13. [PubMed] [Google Scholar]
- Estes D. M., Teale J. M. In vivo effects of anticytokine antibodies on isotype restriction in Mesocestoides corti-infected BALB/c mice. Infect Immun. 1991 Mar;59(3):836–842. doi: 10.1128/iai.59.3.836-842.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hammerberg B., Williams J. F. Interaction between Taenia taeniaeformis and the complement system. J Immunol. 1978 Mar;120(3):1033–1038. [PubMed] [Google Scholar]
- Hayunga E. G., Sumner M. P., Letonja T. Evidence for selective incorporation of host immunoglobulin by strobilocerci of Taenia taeniaeformis. J Parasitol. 1989 Aug;75(4):638–642. [PubMed] [Google Scholar]
- Johnson K. S., Harrison G. B., Lightowlers M. W., O'Hoy K. L., Cougle W. G., Dempster R. P., Lawrence S. B., Vinton J. G., Heath D. D., Rickard M. D. Vaccination against ovine cysticercosis using a defined recombinant antigen. Nature. 1989 Apr 13;338(6216):585–587. doi: 10.1038/338585a0. [DOI] [PubMed] [Google Scholar]
- Kalinna B., McManus D. P. An IgG (Fc gamma)-binding protein of Taenia crassiceps (Cestoda) exhibits sequence homology and antigenic similarity with schistosome paramyosin. Parasitology. 1993 Apr;106(Pt 3):289–296. doi: 10.1017/s0031182000075119. [DOI] [PubMed] [Google Scholar]
- Kunz J., Kalinna B., Watschke V., Geyer E. Taenia crassiceps metacestode vesicular fluid antigens shared with the Taenia solium larval stage and reactive with serum antibodies from patients with neurocysticercosis. Zentralbl Bakteriol. 1989 Oct;271(4):510–520. doi: 10.1016/s0934-8840(89)80113-6. [DOI] [PubMed] [Google Scholar]
- Laclette J. P., Shoemaker C. B., Richter D., Arcos L., Pante N., Cohen C., Bing D., Nicholson-Weller A. Paramyosin inhibits complement C1. J Immunol. 1992 Jan 1;148(1):124–128. [PubMed] [Google Scholar]
- Landa A., Laclette J. P., Nicholson-Weller A., Shoemaker C. B. cDNA cloning and recombinant expression of collagen-binding and complement inhibitor activity of Taenia solium paramyosin (AgB). Mol Biochem Parasitol. 1993 Aug;60(2):343–347. doi: 10.1016/0166-6851(93)90147-p. [DOI] [PubMed] [Google Scholar]
- Leid R. W., Grant R. F., Suquet C. M. Inhibition of equine neutrophil chemotaxis and chemokinesis by a Taenia taeniaeformis proteinase inhibitor, taeniaestatin. Parasite Immunol. 1987 Mar;9(2):195–204. doi: 10.1111/j.1365-3024.1987.tb00500.x. [DOI] [PubMed] [Google Scholar]
- Leid R. W., Grant R. F., Suquet C. M. Inhibition of neutrophil aggregation by taeniaestatin, a cestode proteinase inhibitor. Int J Parasitol. 1987 Oct;17(7):1349–1353. doi: 10.1016/0020-7519(87)90102-0. [DOI] [PubMed] [Google Scholar]
- Leid R. W., McConnell L. A. PGE2 generation and release by the larval stage of the cestode, taenia taeniaeformis. Prostaglandins Leukot Med. 1983 Jul;11(3):317–323. doi: 10.1016/0262-1746(83)90043-4. [DOI] [PubMed] [Google Scholar]
- Leid R. W., Suquet C. M. A superoxide dismutase of metacestodes of Taenia taeniaeformis. Mol Biochem Parasitol. 1986 Mar;18(3):301–311. doi: 10.1016/0166-6851(86)90087-3. [DOI] [PubMed] [Google Scholar]
- Leid R. W., Suquet C. M., Tanigoshi L. Oxygen detoxifying enzymes in parasites: a review. Acta Leiden. 1989;57(2):107–114. [PubMed] [Google Scholar]
- Letonja T., Hammerberg B. Third component of complement, immunoglobulin deposition, and leucocyte attachment related to surface sulfate on larval Taenia taeniaeformis. J Parasitol. 1983 Aug;69(4):637–644. [PubMed] [Google Scholar]
- Lewis D. E., Minshall M., Wray N. P., Paddock S. W., Smith L. C., Crane M. M. Confocal microscopic detection of human immunodeficiency virus RNA-producing cells. J Infect Dis. 1990 Dec;162(6):1373–1378. doi: 10.1093/infdis/162.6.1373. [DOI] [PubMed] [Google Scholar]
- McManus D. P., Lamsam S. Taenia crassiceps surface immunoglobulins: parasite- or host-derived? Parasitology. 1990 Aug;101(Pt 1):127–137. doi: 10.1017/s003118200007983x. [DOI] [PubMed] [Google Scholar]
- Mitchell G. F., Goding J. W., Rickard M. D. Studies on immune responses to larval cestodes in mice. Increased susceptibility of certain mouse strains and hypothymic mice to Taenia taeniaeformis and analysis of passive transfer of resistance with serum. Aust J Exp Biol Med Sci. 1977 Apr;55(2):165–186. doi: 10.1038/icb.1977.13. [DOI] [PubMed] [Google Scholar]
- Molinari J. L., Meza R., Tato P. Taenia solium: cell reactions to the larva (Cysticercus cellulosae) in naturally parasitized, immunized hogs. Exp Parasitol. 1983 Dec;56(3):327–338. doi: 10.1016/0014-4894(83)90078-4. [DOI] [PubMed] [Google Scholar]
- Molinari J. L., Tato P., Lara-Aguilera R., White A. C., Jr Effects of serum from neurocysticercosis patients on the structure and viability of Taenia solium oncospheres. J Parasitol. 1993 Feb;79(1):124–127. [PubMed] [Google Scholar]
- Paddock S., Mahoney S., Minshall M., Smith L., Duvic M., Lewis D. Improved detection of in situ hybridization by laser scanning confocal microscopy. Biotechniques. 1991 Oct;11(4):486–493. [PubMed] [Google Scholar]
- Pearce E. J., Caspar P., Grzych J. M., Lewis F. A., Sher A. Downregulation of Th1 cytokine production accompanies induction of Th2 responses by a parasitic helminth, Schistosoma mansoni. J Exp Med. 1991 Jan 1;173(1):159–166. doi: 10.1084/jem.173.1.159. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Reiner S. L., Locksley R. M. The regulation of immunity to Leishmania major. Annu Rev Immunol. 1995;13:151–177. doi: 10.1146/annurev.iy.13.040195.001055. [DOI] [PubMed] [Google Scholar]
- Rickard M. D., Harrison G. B., Heath D. D., Lightowlers M. W. Taenia ovis recombinant vaccine--'quo vadit'. Parasitology. 1995;110 (Suppl):S5–S9. doi: 10.1017/s0031182000001438. [DOI] [PubMed] [Google Scholar]
- Sanz C. R. Host response in childhood neurocysticercosis. Some pathological aspects. Childs Nerv Syst. 1987;3(4):206–207. doi: 10.1007/BF00274046. [DOI] [PubMed] [Google Scholar]
- Sciutto E., Fragoso G., Baca M., De la Cruz V., Lemus L., Lamoyi E. Depressed T-cell proliferation associated with susceptibility to experimental Taenia crassiceps infection. Infect Immun. 1995 Jun;63(6):2277–2281. doi: 10.1128/iai.63.6.2277-2281.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Siebert A. E., Jr, Good A. H. Taenia crassiceps: effect of normal and immune serum on metacestodes in vitro. Exp Parasitol. 1979 Aug;48(1):164–174. doi: 10.1016/0014-4894(79)90065-1. [DOI] [PubMed] [Google Scholar]
- Suquet C., Green-Edwards C., Leid R. W. Isolation and partial characterization of a Taenia taeniaeformis metacestode proteinase inhibitor. Int J Parasitol. 1984 Apr;14(2):165–172. doi: 10.1016/0020-7519(84)90044-4. [DOI] [PubMed] [Google Scholar]
- Tato P., Castro A. M., Rodríguez D., Soto R., Arechavaleta F., Molinari J. L. Suppression of murine lymphocyte proliferation induced by a small RNA purified from the Taenia solium metacestode. Parasitol Res. 1995;81(3):181–187. doi: 10.1007/BF00937107. [DOI] [PubMed] [Google Scholar]
- Villa O. F., Kuhn R. E. Mice infected with the larvae of Taenia crassiceps exhibit a Th2-like immune response with concomitant anergy and downregulation of Th1-associated phenomena. Parasitology. 1996 Jun;112(Pt 6):561–570. doi: 10.1017/s0031182000066142. [DOI] [PubMed] [Google Scholar]
- White A. C., Jr Neurocysticercosis: a major cause of neurological disease worldwide. Clin Infect Dis. 1997 Feb;24(2):101–115. doi: 10.1093/clinids/24.2.101. [DOI] [PubMed] [Google Scholar]
- White A. C., Jr, Robinson P., Kuhn R. Taenia solium cysticercosis: host-parasite interactions and the immune response. Chem Immunol. 1997;66:209–230. [PubMed] [Google Scholar]
- Wynn T. A., Cheever A. W. Cytokine regulation of granuloma formation in schistosomiasis. Curr Opin Immunol. 1995 Aug;7(4):505–511. doi: 10.1016/0952-7915(95)80095-6. [DOI] [PubMed] [Google Scholar]
- Zakroff S. G., Beck L., Platzer E. G., Spiegelberg H. L. The IgE and IgG subclass responses of mice to four helminth parasites. Cell Immunol. 1989 Mar;119(1):193–201. doi: 10.1016/0008-8749(89)90235-9. [DOI] [PubMed] [Google Scholar]
- Zhu Y., Lukacs N. W., Boros D. L. Cloning of TH0- and TH2-type helper lymphocytes from liver granulomas of Schistosoma mansoni-infected mice. Infect Immun. 1994 Mar;62(3):994–999. doi: 10.1128/iai.62.3.994-999.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- de Aluja A. S., González D., Rodríguez Carbajal J., Flisser A. Histological description of tomographic images of Taenia solium cysticerci in pig brains. Clin Imaging. 1989 Dec;13(4):292–298. doi: 10.1016/0899-7071(89)90062-4. [DOI] [PubMed] [Google Scholar]
- de Aluja A., Vargas G. The histopathology of porcine cysticercosis. Vet Parasitol. 1988 Apr;28(1-2):65–77. doi: 10.1016/0304-4017(88)90019-2. [DOI] [PubMed] [Google Scholar]