Abstract
BACKGROUND: Aging is associated with several alterations in the phenotype, repertoire and activation status of lymphocytes as well as in the cytokine profile produced by these cells. As a lifelong condition, chronic parasitic diseases such as human schistosomiasis overlaps with the aging process and no systematic study has yet addressed the changes in immune response during infection with Schistosoma mansoni in older individuals. AIM: Herein we study the influence of immunological alterations brought about by senescence in the course of schistosomiasis. MATERIALS AND METHODS: Individuals 10-95 years of age, from both sexes, from an endemic area for S. mansoni infection were matched by intensity of infection as measured by egg counts. We analyzed, as a parameter, cytokine expression by lymphocytes and natural killer cells after in vitro stimulation with soluble egg antigen and soluble worm antigen using flow cytometry. RESULTS: We demonstrated that the frequency of CD16+ interferon-gamma (IFN-gamma)+ natural killer cells in negative individuals over the age of 70 years is significantly higher than in positive individuals after in vitro stimulation with S. mansoni antigen extracts. The frequency of these cells is increased in all individuals over the age of 50 years and only declines in positive individuals after 70 years of age. Analysis of either CD4? or CD8? cells after antigen stimulation show no significant increase in frequency of IFN-gamma in negative or in positive individuals of this age group, suggesting that the effect on CD16+ cells is not T-cell dependent. CONCLUSION: Since production of IFN-gamma has been related to resistance to schistosome infection, our data suggest that age-associated changes in CD16+ cells may play a role in controlling infection intensity in the elderly in S. mansoni endemic areas of Brazil.
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- Amiri P., Haak-Frendscho M., Robbins K., McKerrow J. H., Stewart T., Jardieu P. Anti-immunoglobulin E treatment decreases worm burden and egg production in Schistosoma mansoni-infected normal and interferon gamma knockout mice. J Exp Med. 1994 Jul 1;180(1):43–51. doi: 10.1084/jem.180.1.43. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Anderson S., Shires V. L., Wilson R. A., Mountford A. P. In the absence of IL-12, the induction of Th1-mediated protective immunity by the attenuated schistosome vaccine is impaired, revealing an alternative pathway with Th2-type characteristics. Eur J Immunol. 1998 Sep;28(9):2827–2838. doi: 10.1002/(SICI)1521-4141(199809)28:09<2827::AID-IMMU2827>3.0.CO;2-K. [DOI] [PubMed] [Google Scholar]
- Asseman C., Pancré V., Quatennens B., Auriault C. Schistosoma mansoni-infected mice show augmented hepatic fibrosis and selective inhibition of liver cytokine production after treatment with anti-NK1.1 antibodies. Immunol Lett. 1996 Dec 1;54(1):11–20. doi: 10.1016/s0165-2478(96)02634-x. [DOI] [PubMed] [Google Scholar]
- Bahia-Oliveira L. M., Gazzinelli G., Eloi-Santos S. M., Cunha-Melo J. R., Alves-Oliveira L. F., Silveira A. M., Viana I. R., Carmo J., Souza A., Correa-Oliveira R. Differential cellular reactivity to adult worm antigens of patients with different clinical forms of schistosomiasis mansoni. Trans R Soc Trop Med Hyg. 1992 Jan-Feb;86(1):57–61. doi: 10.1016/0035-9203(92)90441-e. [DOI] [PubMed] [Google Scholar]
- Bethony J., Williams J. T., Blangero J., Kloos H., Gazzinelli A., Soares-Filho B., Coelho L., Alves-Fraga L., Williams-Blangero S., Loverde P. T. Additive host genetic factors influence fecal egg excretion rates during Schistosoma mansoni infection in a rural area in Brazil. Am J Trop Med Hyg. 2002 Oct;67(4):336–343. doi: 10.4269/ajtmh.2002.67.336. [DOI] [PubMed] [Google Scholar]
- Brito C. F., Caldas I. R., Coura Filho P., Correa-Oliveira R., Oliveira S. C. CD4+ T cells of schistosomiasis naturally resistant individuals living in an endemic area produce interferon-gamma and tumour necrosis factor-alpha in response to the recombinant 14KDA Schistosoma mansoni fatty acid-binding protein. Scand J Immunol. 2000 Jun;51(6):595–601. doi: 10.1046/j.1365-3083.2000.00710.x. [DOI] [PubMed] [Google Scholar]
- Corrêa-Oliveira R., Malaquias L. C., Falcão P. L., Viana I. R., Bahia-Oliveira L. M., Silveira A. M., Fraga L. A., Prata A., Coffman R. L., Lambertucci J. R. Cytokines as determinants of resistance and pathology in human Schistosoma mansoni infection. Braz J Med Biol Res. 1998 Jan;31(1):171–177. doi: 10.1590/s0100-879x1998000100024. [DOI] [PubMed] [Google Scholar]
- Cossarizza A., Ortolani C., Monti D., Franceschi C. Cytometric analysis of immunosenescence. Cytometry. 1997 Apr 1;27(4):297–313. doi: 10.1002/(sici)1097-0320(19970401)27:4<297::aid-cyto1>3.0.co;2-a. [DOI] [PubMed] [Google Scholar]
- Cutts L., Wilson R. A. Elimination of a primary schistosome infection from rats coincides with elevated IgE titres and mast cell degranulation. Parasite Immunol. 1997 Feb;19(2):91–102. doi: 10.1046/j.1365-3024.1997.d01-184.x. [DOI] [PubMed] [Google Scholar]
- Falcão P. L., Malaquias L. C., Martins-Filho O. A., Silveira A. M., Passos V. M., Prata A., Gazzinelli G., Coffman R. L., Correa-Oliveira R. Human Schistosomiasis mansoni: IL-10 modulates the in vitro granuloma formation. Parasite Immunol. 1998 Oct;20(10):447–454. doi: 10.1046/j.1365-3024.1998.00166.x. [DOI] [PubMed] [Google Scholar]
- Franceschi C., Bonafè M., Valensin S. Human immunosenescence: the prevailing of innate immunity, the failing of clonotypic immunity, and the filling of immunological space. Vaccine. 2000 Feb 25;18(16):1717–1720. doi: 10.1016/s0264-410x(99)00513-7. [DOI] [PubMed] [Google Scholar]
- Gazzinelli A., Bethony J., Fraga L. A., LoVerde P. T., Correa-Oliveira R., Kloos H. Exposure to Schistosoma mansoni infection in a rural area of Brazil. I: water contact. Trop Med Int Health. 2001 Feb;6(2):126–135. doi: 10.1046/j.1365-3156.2001.00684.x. [DOI] [PubMed] [Google Scholar]
- Gazzinelli G., Viana I. R., Bahia-Oliveira L. M., Silveira A. M., Queiroz C. C., Carvalho O. dos S., Massara C. L., Fraga L. A., Colley D. G., Correa-Oliveira R. Immunological profiles of patients from endemic areas infected with Schistosoma mansoni. Mem Inst Oswaldo Cruz. 1992;87 (Suppl 4):139–142. doi: 10.1590/s0074-02761992000800020. [DOI] [PubMed] [Google Scholar]
- Henri Sandrine, Chevillard Christophe, Mergani Adil, Paris Patricia, Gaudart Jean, Camilla Christophe, Dessein Hélia, Montero Felix, Elwali Nasr-Eldin M. A., Saeed Osman K. Cytokine regulation of periportal fibrosis in humans infected with Schistosoma mansoni: IFN-gamma is associated with protection against fibrosis and TNF-alpha with aggravation of disease. J Immunol. 2002 Jul 15;169(2):929–936. doi: 10.4049/jimmunol.169.2.929. [DOI] [PubMed] [Google Scholar]
- Hodes R. J. Aging and the immune system. Immunol Rev. 1997 Dec;160:5–8. doi: 10.1111/j.1600-065x.1997.tb01022.x. [DOI] [PubMed] [Google Scholar]
- Hoffmann Karl F., Wynn Thomas A., Dunne David W. Cytokine-mediated host responses during schistosome infections; walking the fine line between immunological control and immunopathology. Adv Parasitol. 2002;52:265–307. doi: 10.1016/s0065-308x(02)52014-5. [DOI] [PubMed] [Google Scholar]
- Katz N., Chaves A., Pellegrino J. A simple device for quantitative stool thick-smear technique in Schistosomiasis mansoni. Rev Inst Med Trop Sao Paulo. 1972 Nov-Dec;14(6):397–400. [PubMed] [Google Scholar]
- King C. L., Xianli J., Malhotra I., Liu S., Mahmoud A. A., Oettgen H. C. Mice with a targeted deletion of the IgE gene have increased worm burdens and reduced granulomatous inflammation following primary infection with Schistosoma mansoni. J Immunol. 1997 Jan 1;158(1):294–300. [PubMed] [Google Scholar]
- Malaquias L. C., Falcão P. L., Silveira A. M., Gazzinelli G., Prata A., Coffman R. L., Pizziolo V., Souza C. P., Colley D. G., Correa-Oliveira R. Cytokine regulation of human immune response to Schistosoma mansoni: analysis of the role of IL-4, IL-5 and IL-10 on peripheral blood mononuclear cell responses. Scand J Immunol. 1997 Oct;46(4):393–398. doi: 10.1046/j.1365-3083.1997.d01-136.x. [DOI] [PubMed] [Google Scholar]
- Martins-Filho O. A., Dutra W. O., Freeman G. L., Silveira A. M., Rabello A., Colley D. G., Prata A., Gazzinelli G., Correa-Oliveira R., Carvalho-Parra J. Flow cytometric study of blood leucocytes in clinical forms of human schistosomiasis. Scand J Immunol. 1997 Sep;46(3):304–311. doi: 10.1046/j.1365-3083.1997.d01-119.x. [DOI] [PubMed] [Google Scholar]
- Medzhitov Ruslan, Janeway Charles A., Jr Decoding the patterns of self and nonself by the innate immune system. Science. 2002 Apr 12;296(5566):298–300. doi: 10.1126/science.1068883. [DOI] [PubMed] [Google Scholar]
- Olsson J., Wikby A., Johansson B., Löfgren S., Nilsson B. O., Ferguson F. G. Age-related change in peripheral blood T-lymphocyte subpopulations and cytomegalovirus infection in the very old: the Swedish longitudinal OCTO immune study. Mech Ageing Dev. 2000 Dec 20;121(1-3):187–201. doi: 10.1016/s0047-6374(00)00210-4. [DOI] [PubMed] [Google Scholar]
- Pawelec G., Solana R. Immunoageing - the cause or effect of morbidity. Trends Immunol. 2001 Jul;22(7):348–349. doi: 10.1016/s1471-4906(01)01956-1. [DOI] [PubMed] [Google Scholar]
- Sansoni P., Cossarizza A., Brianti V., Fagnoni F., Snelli G., Monti D., Marcato A., Passeri G., Ortolani C., Forti E. Lymphocyte subsets and natural killer cell activity in healthy old people and centenarians. Blood. 1993 Nov 1;82(9):2767–2773. [PubMed] [Google Scholar]
- Sher A., James S. L., Correa-Oliveira R., Hieny S., Pearce E. Schistosome vaccines: current progress and future prospects. Parasitology. 1989;98 (Suppl):S61–S68. doi: 10.1017/s0031182000072255. [DOI] [PubMed] [Google Scholar]
- Solana R., Alonso M. C., Peña J. Natural killer cells in healthy aging. Exp Gerontol. 1999 Jun;34(3):435–443. doi: 10.1016/s0531-5565(99)00008-x. [DOI] [PubMed] [Google Scholar]
- Solana R., Mariani E. NK and NK/T cells in human senescence. Vaccine. 2000 Feb 25;18(16):1613–1620. doi: 10.1016/s0264-410x(99)00495-8. [DOI] [PubMed] [Google Scholar]
- Song H., Price P. W., Cerny J. Age-related changes in antibody repertoire: contribution from T cells. Immunol Rev. 1997 Dec;160:55–62. doi: 10.1111/j.1600-065x.1997.tb01027.x. [DOI] [PubMed] [Google Scholar]
- Spencer N. F., Poynter M. E., Hennebold J. D., Mu H. H., Daynes R. A. Does DHEAS restore immune competence in aged animals through its capacity to function as a natural modulator of peroxisome activities? Ann N Y Acad Sci. 1995 Dec 29;774:200–216. doi: 10.1111/j.1749-6632.1995.tb17382.x-i1. [DOI] [PubMed] [Google Scholar]
- Stadecker M. J. The development of granulomas in schistosomiasis: genetic backgrounds, regulatory pathways, and specific egg antigen responses that influence the magnitude of disease. Microbes Infect. 1999 Jun;1(7):505–510. doi: 10.1016/s1286-4579(99)80089-6. [DOI] [PubMed] [Google Scholar]
- Viana I. R., Sher A., Carvalho O. S., Massara C. L., Eloi-Santos S. M., Pearce E. J., Colley D. G., Gazzinelli G., Correa-Oliveira R. Interferon-gamma production by peripheral blood mononuclear cells from residents of an area endemic for Schistosoma mansoni. Trans R Soc Trop Med Hyg. 1994 Jul-Aug;88(4):466–470. doi: 10.1016/0035-9203(94)90436-7. [DOI] [PubMed] [Google Scholar]
- Webster M., Correa-Oliveira R., Gazzinelli G., Viana I. R., Fraga L. A., Silveira A. M., Dunne D. W. Factors affecting high and low human IgE responses to schistosome worm antigens in an area of Brazil endemic for Schistosoma mansoni and hookworm. Am J Trop Med Hyg. 1997 Oct;57(4):487–494. doi: 10.4269/ajtmh.1997.57.487. [DOI] [PubMed] [Google Scholar]
- Webster M., Roberts M., Fulford A. J., Marguerite M., Gallisot M. C., Diagne M., Niang M., Riveau G., Capron A., Dunne D. W. Human IgE responses to rSm22.6 are associated with infection intensity rather than age per se, in a recently established focus of Schistomiasis mansoni. Trop Med Int Health. 1998 Apr;3(4):318–326. doi: 10.1046/j.1365-3156.1998.00234.x. [DOI] [PubMed] [Google Scholar]
- Weksler M. E., Szabo P. The effect of age on the B-cell repertoire. J Clin Immunol. 2000 Jul;20(4):240–249. doi: 10.1023/a:1006659401385. [DOI] [PubMed] [Google Scholar]
- Wolowczuk I., Auriault C., Gras-Masse H., Vendeville C., Balloul J. M., Tartar A., Capron A. Protective immunity in mice vaccinated with the Schistosoma mansoni P-28-1 antigen. J Immunol. 1989 Feb 15;142(4):1342–1350. [PubMed] [Google Scholar]
- van Der Kleij D., Tielens A. G., Yazdanbakhsh M. Recognition of schistosome glycolipids by immunoglobulin E: possible role in immunity. Infect Immun. 1999 Nov;67(11):5946–5950. doi: 10.1128/iai.67.11.5946-5950.1999. [DOI] [PMC free article] [PubMed] [Google Scholar]
