Abstract
To understand the host-parasite relationship in histoplasmosis, mice were inoculated with histoplasmin (HP), the filtrate of aged cultures of Histoplasma capsulatum, and the immune response of these mice towards sheep red blood cells (SRBC) and to trinitrophenyl hapten was studied. The filtrate abrogated completely the primary antibody response to both antigens as measured by the number of spleen hemolytic plaque forming cells when HP was administered at doses greater than 200 ⧎g two days before the antigen. Suppression was elicited by HP when it was injected either intravenously, intraperitoneally, or subcutaneously. Inoculation with HP and antigen on the same day did not result in suppression. The secondary antibody response was not modified at any dose. Variation of the response with time was determined by counting the number of rosette forming cells (RFC) to SRBC every two days for a total of 21 days. Antibody-mediated RFC (‘B’ rosettes) were depressed throughout the experiment, while the number of non ‘B’, presumably T, RFC did not vary from control values. In animals inoculated with HP alone, high numbers of RFC were detected on day 11 after HP inoculation, suggesting that HP may have polyclonal activation effects. These results support the possibility that H. capsulatum evades the immune defenses by induction of a suppressive phenomenon in which the afferent limb of the immune response is not involved. This effect appeared to be induced directly by a product of the fungus, instead of by factors generated during the immune response to this microorganism.
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Abbreviations
- HP:
-
histoplasmin
- SRBC:
-
sheep red blood cells
- RFC:
-
rosette forming cells
- ‘B’ rosettes:
-
antibody-mediated RFC
- PBS:
-
phosphate-buffered saline
- HBSS:
-
Hank's balanced salt solution
- BRBC:
-
burro red blood cells
- TNP:
-
trinitrophenyl
- i.p.:
-
intraperitoneally
- s.c.:
-
subcutaneously
- i.v.:
-
intravenously
- PFC:
-
plaque forming cells
References
Artz RP, Bullock WE. Immunoregulatory response in experimental disseminated Histoplasmosis: depression of T-cell dependent and T-effector responses by activation of splenic suppressor cells. Infect Immun 1979; 23:893–902.
Artz RP, Jacobson R, Bullock WE. Decreased suppressor cell activity in disseminated granulomatous infections. Clin Exp Immunol 1980; 41:343–52.
Avrameas S, Tandou B, Chuilon S. Glutaraldehyde, cyanuric chloride and tetrazotized O-dianisidine as coupling reagents in the passive hemagglutination test. Immunochemistry 1969; 6:67–76.
Bona C, Chedid L, Cuarbaru P, Shek P, Dubisky S, Cinader B. Blastoid transformation for rabbit B derived lymphocytes by a mitogen extracted from nocardia. J Immunol 1975; 114:348–53.
Bullock WE, Artz RP, Bhathena D, Tung KSK. Histoplasmosis: association with circulating immune complexes, eosinophila and mesangiophatic glomerulonefritis. Arch Int Med 1979; 139:700–2.
Calcagno M, Pérez J R, Waldo MG, Cabrera G, Weiss-Steider B. Evidence of the existence of a factor that induces Fc receptors on bone marrow cells. Blood 1982; 59:756–60.
Calderon RA, Cordoba F. Immunosuppressive activity of Phaseolus coccineus and Phaseolus vulgaris extracts in mice. Eur J Immunol 1976; 6:522–25.
Carvajal R, Ruiz B, Barjau E. Immunosuppressive effect of Entamoeba histolytica extract on hamsters. Z. Parasitenkd 1983; 69:183–89.
Cavaillon JM, Leclerc C, Alouf JE. Polyclonal antibody forming cell activation and immunomodulation of the in vitro immune response induced by streptococcal extracellular products. Cell Immunol 1983; 76:200–6.
Clayton EC, Sachs DL, Ogilvie BM, Askonas BA. Membrane fractions of trypanosomes mimic the immunosuppressive and mitogenic effect of living parasites on the host. Parasite Immunol 1979; 1:241–49.
Cozad GC. A study of the whole yeast cell agglutination test in rabbit experimentally infected with Histoplasma capsulatum. J Immunol 1958; 81:368–75.
Deepe GS, Kravitz GR, Bullock WE. Pharmacological modulation of suppressor cell activity in mice with disseminated histoplasmosis. Infect Immun 1983; 41:114–20.
Deepe GS, Watson SR, Bullock WE. Generation of disparate immunoregulatory factors in two inbred strains of mice with disseminated histoplasmosis. J Immunol 1982; 129:2186–91.
Deepe GS, Watson SR, Bullock WE. Cellular origins and target cells of immunoregulatory factors in mice with disseminated histoplasmosis. J Immunol 1984; 132:2064–71.
Deepe GS, Smith JG, Sonnenfeld G, Denman D, Bullock WE. Development and characterization of Histoplasma capsulatum-reactive murine T-cell lines and clones. Infect Immun 1986; 54:714–22.
Deepe GS, Taylor CL, Harris JE, Bullock WE. Modulation of cellular immune response in mice with disseminated histoplasmosis by recombinant interleukin-2. Infect Immun 1986; 53:6–12.
Diamanstein T, Keppler W, Blinstein-Willinger E, Ben-Efraim S. Suppression of the primary immune response in vivo to sheep red blood cells by B-cell mitogens. Immunology 1976; 30:401–7.
Dresser DW, Greaves MF. Assays for antibody producing cells. In: Weir DW, ed. Handbook of experimental immunology, 3rd ed. Oxford: Blackwell Sci Pub, 1973; 27:9–27.
Egan HS, Reeder WJ, Eksten RD. Effect of concanavalin A in vivo in suppressing the antibody response in mice. J Immunol 1974; 112:63–69.
Elnner JJ. Suppressor adherent cells in human tuberculosis. J Immunol 1978; 121:1573–79.
Ford WL. The preparation and labelling of lymphocytes. In: Weir DM ed. Handbook of experimental immunology. 3rd ed. Oxford: Blackwell Sci Pub, 1978; 23:1–23.
Golub ES, Mishell RI, Weigle WO, Dutton RW. A modification of the hemolytic plaque assay for use with protein antigens. J Immunol 1968; 100:133–37.
Goodwin RA, Shapiro JL, Grafton HT, Stephen ST, Despres RM. Disseminated histoplasmosis, clinical and pathological correlations. Medicine 1980; 52:1–33.
Grage JM, Gibson J, Nassau E. Enzyme-linked immunosorbent assay (ELISA): a study of antibodies to Mycobacterium tuberculosis in the IgG, IgA and IgM classes in tuberculosis, sarcoidosis and Crohn's disease. Tubercle 1980; 61:145–52.
Hanna EE, Watson DW. Enhanced immune response after immunosuppression by a streptococcal pyrogenic exotoxin. Infect Immun 1973; 7:1009–11.
Ho MK, Morse SI, Kong AS. Studies on a new lymphocyte mitogen from Bordetella pertussis. J Exp Med 1981; 153:75–88.
Jerne JK, Nordin AA. Plaque formation in agar by single antibody producing cells. Science 1963; 140:405–7.
Katz DH. Surface immunoglobulin on lymphocytes. In: Dixon FJ, Kunkel HG, eds. Lymphocyte differentiation, recognition and regulation; Immunology, International Series. New York: Academic Press, 1977: 152–87.
Kontianen S, Feldman M. Suppressor cell induction in vitro. I. Kinetics of induction of antigen specific suppressor cells. Eur J Immunol 1976; 6:296–301.
Lowry OH, Rosebrough JJ, Farr AL, Randall RJ. Protein measurement with the folin phenol serial reagent. J Biol Chem 1951; 193:265–75.
Mehra V, Mason LH, Reinhers NE, Schlossman SF, Bloom BR. Delineation of a human T cell subset responsible for lepromin-induced suppression in leprosy patients. J Immunol 1980; 125:1183–88.
Möller ER, Bullock WW, Mäkelä O. Affinity of T and B lymphocyte receptors for hapten determinants. Eur J Immunol 1973; 3:172–79.
Murphy JW, Moorhead JW. Regulation of cell-mediated immunity in cryptococcosis antigen. J Immunol 1982; 128:276–83.
Newberry WM, Chandler JW, Chin TDY, Kirkpatrick CH. Immunology of the mycosis. I. Depressed lymphocyte transformation in chronic histoplasmosis. J Immunol 1968; 100:136–43.
Nickerson DA, Havens RA, Bullock WE. Immunoregulation in disseminated histoplasmosis. Characterization of splenic suppressor cell populations. Cell Immunol 1981; 60:287–97.
Playfair JHL. Suppressor cells in infectious disease. Parasite Immunol 1982; 4:299–304.
Pross HF, Eidinger D. Antigenic competition: a review of non-specific antigen-induced suppression. Adv Immunol 1974; 18:133–68.
Rittenberg MB, Pratt KL. Anti-TNP plaque assay. Primary response of Balb/c mice to soluble and particulated immunogen. Proc Soc Exp Biol Med 1969; 132:575–81.
Ruiz BH, Carbajal RE. Immunomodulation by Histoplasma capsulatum products: Polyclonal activation and mitogenic effects. Mycopathologia 1986; 93:113–19.
Sano K, Sugimoto M, Yasuda T, Egashira Y, Yamada M. Recognition of heterologous cells by macrophages. Microbiol Immunol 1980; 24:957–67.
Sher DKG, Ju TS, Dorf ME. Hapten specific T cell responses to 4-hydroxy-3-nitrophenyl acetyl. XII. Fine specificity of anti-idiotypic suppressor T cells (Ts2). J Exp Med 1981; 154:1382–89.
Smith CE, Whiting EC, Baker EE, Rosemberg HG, Beard RR, Saito MT. The use of coccidiodin. Amer Rev Tuberc 1948; 57:330–37.
Smith JW, Utz JP. Progressive disseminated histoplasmosis: a prospective study of 26 patients. Ann Intern Med 1972; 76:557–65.
Stobo JD. Immunosuppression in man. Suppression by macrophages can be mediated by interactions with regulatory T cells. J Immunol 1977; 119:918–24.
Tanabe K, Takada S, Susuki M. Regional depression of delayed hypersensitivity to sheep erythrocytes in mice infected with Plasmodium berghei. J Parasitol 1978; 64:367–68.
Taussing JJ. Antigenic competition. In: Sela M, ed. The antigens, Vol. IV. New York: Academic Press, 1977: 333–68.
Taylor JR, Bojalil LF. Immunología de la Histoplasmosis: Aislamiento de un complejo polisacárido-proteina, con actividad immunoespecífica a partir de H. capsulatum. Arch Inv Med (Mex) 1977; 8:91–102.
Taylor ML, Díaz S, González PA, Sosa Ac, Toriello C. Relationship between pathogenesis and immune regulation mechanisms in histoplasmosis: A hypothetical approach. Rev Infect Dis 1984; 6:775–82.
Tewari RP, Khardori N, McConnachie P, von Behren LA, Yamada T. Blastogenic response of lymphocytes from mice immunized by sublethal infection with yeast cells of Histoplasma capsulatum. Infect Immun 1982; 36:1013–18.
Watson SR, Bullock WE. Immunoregulation in disseminated histoplasmosis: Characterization of the surface phenotype of splenic suppressor T lymphocytes. Infect Immun 1982; 37:940–45.
Watson SR, Miller TB, Redington TJ, Bullock WE. Immunoregulation in experimental disseminated histoplasmosis; Flow microfluorometry (FMF) studies of the Thy and Lty phenotypes of T lymphocytes from infected mice. J Immunol 1983; 131:984–90.
Watson SR, Schmitt SK, Hendricks DE, Bullock WE. Immunoregulation in disseminated murine histoplasmosis: Disturbances in the production of interleukins 1 and 2. J Immunol 1985; 135:3487–93.
Wu-Hsieh B, Howard DH. Inhibition of the intracellular growth of Histoplasma capsulatum by recombinant murine gamma interferon. Infect Immun 1987; 55:1014–16.
Wu-Hsieh B, Zlotnik A, Howard DH. T-cell hybridoma-produced lymphokine that activates macrophages to suppress intracellular growth of Histoplasma capsulatum. Infect Immun 1984; 43:380–85.
Youmans GP. Histoplasmosis, blastomycosis, coccidioidomycosis. In: Youmans GP, Paterson PY, Sommer HM, eds. The biologic and clinical basis of infectious diseases. Philadelphia: WB Saunders Co, 1980: 404–26.
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Ruiz, B.H., Carvajal, R.E. & Ortiz -Ortiz, L. Modifications of the immune response induced by Histoplasma capsulatum products. Mycopathologia 109, 1–9 (1990). https://doi.org/10.1007/BF00436999
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DOI: https://doi.org/10.1007/BF00436999