Stimulation of the Protective Response to Actinomycetoma by Nocardia brasiliensis in Mice Treated with Candida albicans Antigens


Actinomycetoma is a chronic subcutaneous lesion caused by the pathogenic bacterium Nocardia (N.) brasiliensis. Yeast antigens of Candida (C.) albicans increase the interferon (IFN)-γ and TCD4+ cells levels that enhance the phagocytic killing of N. brasiliensis, able to survive inside phagocytes and to grow in clustered colonies that form grains. The aim of this work was to test the effect of a crude protein extract of C. albicans on the levels of IFN-γ producing TCD4+ cells and on the outcome of actinomycetoma lesion. Five BALB/c mice with N. brasiliensis infection at left hind footpad were treated four times every other day with C. albicans crude protein extract (CPE). Five uninfected mice treated with CPE or infected mice treated with sterile phosphate-saline buffer were included as positive and negative control groups, respectively. Footpad thickness was recorded in all groups. Once the treatments were finished, single cell suspensions from blood and spleen were prepared for assessing the amount (%) of IFN-γ producing TCD4+ cells by cytofluorometry; presence of TCD4+ and IFN-γ in footpad sections was detected by immunofluorescence and immunohistochemistry, respectively. By comparison with the negative control group, infected mice treated with CPE had lower footpad thickness, higher percentage of blood and spleen IFN-γ producing TCD4+ cells as well as in situ presence of IFN-γ and TCD4+ cells. These findings showed that CPE from C. albicans displayed an immunoadjuvant activity that enhanced the presence of IFN-γ producing TCD4+ cells and IFN-γ for the resolution of N. brasiliensis actinomycetoma in mice.

Share and Cite:

Palma-Ramos, A. , Espinosa-Antunez, V. , Castrillón-Rivera, L. , Nájera-Medina, O. , Vega-Memije, M. , Arenas-Guzmán, R. , Drago-Serrano, M. and Sainz-Espuñes, T. (2014) Stimulation of the Protective Response to Actinomycetoma by Nocardia brasiliensis in Mice Treated with Candida albicans Antigens. Advances in Microbiology, 4, 297-305. doi: 10.4236/aim.2014.46036.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] van de Sande, W.W. (2013) Global Burden of Human Mycetoma: A Systematic Review and Meta-Analysis. PLOS Neglected Tropical Diseases, 7, e2550.
[2] Lopez-Martinez, R., Mendez-Tovar, L.J., Bonifaz, A., Arenas, R., Mayorga, J., Welsh, O., Vera-Cabrera, L., Padilla-Desgarennes, M.C., Contreras Perez, C., Chavez, G., Estrada, R., Hernandez-Hernandez, F. and Manzano-Gayosso, P. (2013) Update on the Epidemiology of Mycetoma in Mexico. A Review of 3933 Cases. Gaceta Medica de Mexico, 149, 586-592.
[3] Beaman, B.L. and Beaman, L. Nocardia Species: Host-Parasite Relationships. Clinical Microbiology Reviews, 7, 213-264.
[4] Guimaraes, C.C., Castro, L.G. and Sotto, M.N. (2003) Lymphocyte Subsets, Macrophages and Langerhans Cells in Actinomycetoma and Eumycetoma Tissue Reaction. Acta Tropical, 87, 377-384.
[5] Zlotnik, H. and Buckley, H.R. (1980) Experimental Production of Actinomycetoma in BALB/c Mice. 1. Infection and Immunity, 29, 1141-1145.
[6] Salinas-Carmona, M.C., Torres-Lopez, E., Ramos, A.I., Licon-Trillo, A. and Gonzalez-Spencer, D. (1999) Immune response to Nocardiabrasiliensis Antigens in an Experimental Model of Actinomycetoma in BALB/c Mice. Infection and Immunity, 67, 2428-2432.
[7] Solis-Soto, J.M., Quintanilla-Rodriguez, L.E., Meester, I., Segoviano-Ramirez, J.C., Vazquez-Juarez, J.L. and Salinas Carmona, M.C. (2008) In Situ Detection and Distribution of Inflammatory Cytokines during the Course of Infection with Nocardiabrasiliensis. Histology and Histopathology, 23, 573-581.
[8] Rosas-Taraco, A.G., Perez-Linan, A.R., Bocanegra-Ibarias, P., Perez-Rivera, L.I. and Salinas-Carmona, M.C. (2012) Nocardiabrasiliensis Induces an Immunosuppressive Microenvironment That Favors Chronic Infection in BALB/c Mice. Infection and Immunity, 80, 2493-2499.
[9] Trevino-Villarreal, J.H., Vera-Cabrera, L., Valero-Guillen, P.L. and Salinas-Carmona, M.C. (2012) Nocardiabrasiliensis Cell Wall Lipids Modulate Macrophage and Dendritic Responses That Favor Development of Experimental Actinomycetoma in BALB/c Mice. Infection and Immunity, 80, 3587-3601.
[10] Folb, P.I., Jaffe, R. and Altmann, G. (1976) Nocardiaasteroides and Nocardiabrasiliensis Infections in Mice. 1. Infection and Immunity, 13, 1490-1496.
[11] Palma-Ramos, A., Cuevas-Moreno, M.A., Castrillon-Rivera, L.E., Vega-Memije, M.E. and Arenas-Guzman, R. (2010) Estudio longitudinal de mediadores proinflamatorios (TNF-α e IL-1β mediante tecnica de ELISA) en lesiones de actinomicetoma provocadas por inoculacion de Nocardiabrasiliensis en ratones Balb/c. Dermatological Review of Mexico, 54, 113-119.
[12] Mendez-Tovar, L.J., Mondragon-Gonzalez, R., Vega-Lopez, F., Dockrell, H.M., Hay, R., Lopez-Martinez, R., Manzano-Gayosso, P., Hernandez-Hernandez, F., Padilla-Desgarennes, C. and Bonifaz, A. (2004) Cytokineproduction and Lymphocyteproliferation in Patients with Nocardiabrasiliensisactinomycetoma. Mycopathologia, 158, 407-414.
[13] Palma-Ramos, A., Castrillon-Rivera, L.E., Becerril-Parra, D.E., Zamora-Alvarado, R., Aguirre-Hernandez, R.M., Espinosa-Antunez, V.K., Gonzalez-Pacheco, J.R. and Padilla-Desgarennes, C. (2012) Estimulacion de celulas mononucleares humanas in Vitro con extracto total y peptidos liberados al medio por Candidaalbicans. Dermatological Review of Mexico, 56, 377-384.
[14] Mencacci, A., Torosantucci, A., Spaccapelo, R., Romani, L., Bistoni, F. and Cassone, A. (1994) A Mannoprotein Constituent of Candida Albicans That Elicits Different Levels of Delayed-Type Hypersensitivity, Cytokine Production, and Anticandidal Protection in Mice. Infection and Immunity, 62, 5353-5360.
[15] Ausiello, C.M., Urbani, F., Gessani, S., Spagnoli, G.C., Gomez, M.J. and Cassone, A. (1993) Cytokine Gene Expression in Human Peripheral Blood Mononuclear Cells Stimulated by Mannoprotein Constituents from Candida Albicans. Infection and Immunity, 61, 4105-4111.
[16] Romagnoli, G., Nisini, R., Chiani, P., Mariotti, S., Teloni, R., Cassone, A. and Torosantucci, A. (2004) The Interaction of Human Dendritic Cells with Yeast and Germ-Tube Forms of Candida albicans Leads to Efficient Fungal Processing, Dendritic Cell Maturation, and Acquisition of a Th1 Response-Promoting Function. Journal of Leukocyte Biology, 75, 117-126.
[17] Iwasaki, A. and Medzhitov, R. (2010) Regulation of Adaptive Immunity by the Innate Immune System. Science, 327, 291-295.
[18] Millan-Chiu, B.E., Hernandez-Hernandez, F., Perez-Torres, A., Mendez-Tovar, L.J. and Lopez-Martinez, R. (2011) In Situ TLR2 and TLR4 Expression in a Murine Model of Mycetoma Caused by Nocardia brasiliensis. FEMS Immunology & Medical Microbiology, 61, 278-287.
[19] Gagliardi, M.C., Teloni, R., Mariotti, S., Bromuro, C., Chiani, P., Romagnoli, G., Giannoni, F., Torosantucci, A. and Nisini, R. (2010) Endogenous PGE2 Promotes the Induction of Human Th17 Responses by Fungal β-Glucan. Journal of Leukocyte Biology, 88, 947-954.
[20] Curtis, M.M. and Way, S.S. (2009) Interleukin-17 in Host Defence against Bacterial, Mycobacterial and Fungal Pathogens. Immunology, 126, 177-185.
[21] Yao, C., Sakata, D., Esaki, Y., Li, Y., Matsuoka, T., Kuroiwa, K., Sugimoto, Y. and Narumiya, S. (2009) Prostaglandin E2-EP4 Signaling Promotes Immune Inflammation through TH1 Celldifferentiation and TH17 Cell Expansion. Nature Medicine, 15, 633-640.
[22] Nisini, R., Torosantucci, A., Romagnoli, G., Chiani, P., Donati, S., Gagliardi, M.C., Teloni, R., Sargentini, V., Mariotti, S., Iorio E. and Cassone, A. (2007) Beta-Glucan of Candida albicans Cell Wall Causes the Subversion of Human Monocyte Differentiation into Dendritic Cells. Journal of Leukocyte Biology, 82, 1136-1142.

Copyright © 2023 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.