Skip to main content
Log in

Effect of macrophage blockade on the resistance of inbred mice toParacoccidioides brasiliensis infection

  • Human And Animal Mycology
  • Published:
Mycopathologia Aims and scope Submit manuscript

Abstract

The effect of macrophage blockade on the natural resistance and on the adaptative immune response of susceptible (B10.D2/oSn) and resistant (A/Sn) mice toParacoccidioides brasiliensis infection was investigated. B10.D2/oSn and A/Sn mice previously injected with colloidal carbon were infected ip with yeast cells to determine the 50% lethal dose, and to evaluate the anatomy and histopathology, macrophage activation, antibody production and DTH reactions. Macrophage blockade rendered both resistant and susceptible mice considerably more susceptible to infection, as evidenced by increased mortality and many disseminated lesions.P. brasiliensis infection and/or carbon treatment increased the ability of macrophages from resistant mice to spread up to 25 days after treatment. In susceptible mice the enhanced spreading capacity induced by carbon treatment was impaired at all assayed periods except at 1 week after infection. Macrophage blockade enhanced DTH reactions in resistant mice, but did not alter these reactions in susceptible mice, which remained anergic. To the contrary, macrophage blockade enhanced specific antibody production by susceptible mice, but did not affect the low levels produced by resistant mice. The effect of macrophage blockade confirms the natural tendency of resistant animals to mount DTH reactions in the course of the disease and the preferential antibody response developed by susceptible mice afterP. brasiliensis infection. On the whole, macrophage functions appear to play a fundamental role in the natural and acquired resistance mechanisms toP. brasiliensis infection.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

Abbreviations

CMI:

cellular-mediated immunity

DTH:

delayed-type hypersensitivity

LD50 :

50% lethal dosis

MPS:

mononuclear phagocytic system

PCM:

paracoccidioidomycosis

SRBC:

sheep red blood cells

References

  1. Wanke B, Londero AT. Epidemiology and paracoccidioidomycosis infection. In: Franco M, Lacaz CS, Restrepo-Moreno A, Del Negro G (eds), Paracoccidioidomycosis. Boca Raton: CRC Press, 1994: 109–20.

    Google Scholar 

  2. Restrepo A, Restrepo M, Restrepo F, Aristizabal LH, Moncada LH, Velez H. Immune responses in paracoccidioidomycosis: A controlled study of 16 patients before and after treatment. Sabouraudia 1978; 16: 151–63.

    PubMed  Google Scholar 

  3. Robledo MA, Graybill JR, Ahrens J, Restrepo A, Drutz DJ, Robledo M. Host defense against experimental paracoccidoidomycosis. Am Rev Respir Dis 1982; 125: 563–7.

    PubMed  Google Scholar 

  4. Brummer E, Restrepo A, Stevens DA, Azzi R, Gomez AM, Hoyos GL, McEwen JG, Cano LE, De Bedout C. Murine model of paracoccidioidomycosis. Production of fatal acute pulmonary or chronic pulmonary and disseminated disease: Immunological and pathological observations. J Exp Pathol 1984; 1: 241–55.

    PubMed  Google Scholar 

  5. Del Negro G, Lacaz CS, Zamith VA, Siqueira, AM. General clinical aspects: polar forms of paracoccidioidomycosis, the disease in childhood. In: Franco M, Lacaz CS, RestrepoMoreno A, Del Negro G (eds), Paracoccidioidomycosis. Boca Raton: CRC Press, 1994: 225–32.

    Google Scholar 

  6. Lacaz CS. South American blastomycosis. An Fac Med Univ Sao Paulo 1956; 29: 7–120.

    Google Scholar 

  7. Fava Netto C, Castro RM, Gonçalves AP, Dillon NL. Ocorrência familiar da blastomicose sul-americana. A propósito de 14 casos. Rev Inst Med Trop São Paulo 1965; 7: 332–6.

    Google Scholar 

  8. Calich VLG, Singer-Vermes LM, Siqueira AM, Burger E. Susceptibility and resistance of inbred mice toParacoccidioides brasiliensis. Br J Exp Pathol 1985; 66: 585–94.

    PubMed  Google Scholar 

  9. Burger E, Singer-Vermes LM, Calich, VLG. The role of C5 in experimental murine paracoccidioidomycosis. J Infect Dis 1985; 152: 425.

    PubMed  Google Scholar 

  10. Allison AC, Harington JS, Birbeck M. An examination of the cytotoxic effects of silica on macrophages. J Exp Med 1966; 124: 141–53.

    PubMed  Google Scholar 

  11. Sabet T, Newlin C, Friedman H. The effect of RES blockade on cellular antibody formation to sheep erythrocytes. Proc Soc Exp Biol Med 1968; 128: 274–8.

    PubMed  Google Scholar 

  12. Sinha BK, Monga DP, Prasad S. Studies on the role of macrophages in experimental candidosis in mice. Mykosen 1987; 30: 105–12.

    PubMed  Google Scholar 

  13. Monga DP. Role of macrophages in resistance of mice to experimental cryptococcosis. Infect Immun 1981; 32: 975–8.

    PubMed  Google Scholar 

  14. Berry CL. The production of disseminated histoplasmosis in the mouse: the effects of changes in reticulo-endothelial function. J Pathol 1969; 97: 441–57.

    PubMed  Google Scholar 

  15. Von Behren LA, Chaudhary S, Khardori N, Rabinovich S, Shu MD, Tewari RP. Effect of silica on the susceptibility of mice to experimental histoplasmosis. RES J Reticuloendothel Soc 1983; 34: 99–111.

    Google Scholar 

  16. Kerr IB, Da Costa SCG, Schaffer GV, Lagrange PH. Paracoccidioidomycosis in silica-treated rats. Immunol Lett 1983; 7: 129–33.

    PubMed  Google Scholar 

  17. Kashino SS, Calich VLG, Burger E, Singer-Vermes LM. In vivo and in vitro characteristics of sixParacoccidioldes brasiliensis strains. Mycopathologia 1985; 92: 173–8.

    PubMed  Google Scholar 

  18. Fava Netto C. Estudos quantitativos sobre a fixação do complemento na blastomicose sul-americana, com antigeno polissacarídico. Arq Cir Clin Exp S Paulo 1955; 18: 197–254.

    Google Scholar 

  19. Berliner MD, Reca ME. Vital staining ofHistoplasma capsulatum with Janus Green B. Sabouraudia 1966; 5: 26–9.

    PubMed  Google Scholar 

  20. Finney DJ. Probit analysis, 3rd ed. Cambridge: Cambridge University Press, 1980.

    Google Scholar 

  21. Fazioli RA, Singer-Vermes LM, Kashino SS, Burger E, Franco MF, Moscardi-Bacchi M, Calich VLG. Delayed-type hypersensitivity response in an isogenic murine model of paracoccidioidomycosis. Mycopathologia 1994; 126: 137–46.

    PubMed  Google Scholar 

  22. Fava Netto C, Vegas VS, Sciannaméa IM, Guarnieri DB. Antígeno polissacarídico doParacoccidioides brasiliensis: estudo do tempo de cultivo doP. brasiliensis, necessário ao preparo do antígeno. Rev Inst Med Trop São Paulo 1969; 11: 177–81.

    Google Scholar 

  23. Mendes-Giannini MJS, Camargo ME, Lacaz CS, Ferreira AW. Immunoenzymatic absorption test for serodiagnosis of paracoccidioidomycosis. J Clin Microbiol 1984; 20: 103–8.

    PubMed  Google Scholar 

  24. Zar JD. Biostatistical analysis. 2nd ed. New Jersey; Prentice-Hall, 1984: 185–251.

    Google Scholar 

  25. Brummer E. Interaction ofParacoccidioides brasiliensis with host defense cells. In: Franco M, Lacaz CS, Restrepo-Moreno A, Del Negro G (eds), Paracoccidioidomycosis. Boca Raton: CRC Press, 1994: 213–23.

    Google Scholar 

  26. Nakanishi H, Horii Y, Terashima K, Fujita K. Effect of macrophage blockade on the resistance to a primaryBrugia pahangi infection of female BALB/c mice. Trop Med Parasitol 1989, 40: 75–6.

    PubMed  Google Scholar 

  27. Calich VLG, Fazioli RA, Teixeira HC, Russo M, Singer-Vermes LM, Burger E, Vaz CAC. Mechanisms of hostresistance toParacoccidioides brasiliensis. In: Torres-Rodriguez JM, ed. Proceedings of the X Congress of the International Society for Human and Animal Mycology — ISHAM, Barcelona: JR Prous Science Publishers, 1988: 154–9.

    Google Scholar 

  28. Dekaris D, Fauve RM, Raynaud M. Delayed hypersensitivity and inhibition of macrophage spreading: in vivo and in vitro studies of tuberculin and streptococcal hypersensitivity in guinea pigs. J Immunol 1969; 103: 1–5.

    PubMed  Google Scholar 

  29. Dekaris D, Smerdel S, Veselic B. Inhibition of macrophage spreading by supernatants of antigen-stimulated sensitized lymphocytes. Eur J Immunol 1971; 1: 402–4.

    PubMed  Google Scholar 

  30. Mazuran R & Silobrcic V. In vitro inhibition of macrophage spreading by antigens and lymphokines: correlation with the footpad test and kinetics of inhibition. Ann Inst Pasteur Immunol 1987; 138: 201–11.

    PubMed  Google Scholar 

  31. Singer-Vermes LM, Caldeira CB, Burger E, Calich VLG. Experimental murine paracoccidioidomycosis: relationship among the dissemination of the infection, humoral and cellular immune responses. Clin Exp Immunol 1993; 94: 75–9.

    PubMed  Google Scholar 

  32. Yoshikai Y, Miake S, Matsumoto T, Nomoto K, Takeya K. Effect of stimulation and blockade of mononuclear phagocyte system on the delayed footpad reaction to SRBC in mice. Immunology 1979; 38: 577–83.

    PubMed  Google Scholar 

  33. Fazioli RA, Calich VLG, Singer-Vermes LM, Kashino SS, Burger E. Standardization of the intradermal test in experimental murine paracoccidioidomycosis. Braz J Med Biol Res 1986; 19: 641A.

  34. Restrepo A. Inmunidad humoral. In: Del Negro G, Lacaz CS, Fiorillo AM (eds), Paracoccidioidomicose: blastomicose sulamericana. São Paulo: Sarvier-Edusp, 1982: 127–33.

    Google Scholar 

  35. Biozzi G, Mouton D, Stiffel C, Bouthillier Y. A major role of the macrophage in quantitative genetic regulation of immunoresponsiveness and antiinfectious immunity. Adv Immunol 1984; 36: 189–234.

    PubMed  Google Scholar 

  36. Calich VLG, Burger E, Kashino SS, Fazioli RA, Singer-Vermes LM. Resistance toParacoccidioides brasiliensis in mice is controlled by a single dominant autosomal gene. Infect Immun 1987; 55: 1919–23.

    PubMed  Google Scholar 

  37. Calich VLG, Singer-Vermes LM, Russo M, Vaz CAC, Burger. E. Immunogenetics in paracoccidioidomycosis. In: Franco M, Lacaz CS, Restrepo-Moreno A, Del Negro G (eds), Paracoccidioidomycosis. Boca Raton: CRC Press, 1994: 151–73.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kashino, S.S., Fazioli, R.d.A., Moscardi-Bacchi, M. et al. Effect of macrophage blockade on the resistance of inbred mice toParacoccidioides brasiliensis infection. Mycopathologia 130, 131–140 (1995). https://doi.org/10.1007/BF01103095

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01103095

Key words

Navigation