AiM  Vol.8 No.3 , March 2018
Insights on Blood Cytokines Production under Different In Vitro Mycobacterial Antigens in Tuberculosis Intestinal Parasites Co Infected Patients
Abstract: Background: The concomitant presence of intestinal parasite infections (IP) and tuberculosis (TB) has relevance. M. tuberculosis immune response is associated with type 1 T helper cell (Th1) while IP is associated with type Th2 cell. However, there are several contradictory reports on cytokine production under coinfection and this could be in association to the mycobacterial antigens used in the studies. Aim: To get insight into the effects of different M. tuberculosis-specific antigens (ESAT-6/CFP-10 and 38 kDa/CFP-10) in generating of appropriate cytokines on peripheral blood mononuclear cells of IPTB co infected patients. Method: ELISA assessed IFN-γ and other 16 cytokines production and plasm IgE. In 18 months, we documented demographic, economic, clinical characteristics and IP frequency in individuals from Brazil. Results: An overall 10/35 (28.5%) were IPTB co infected and 40/76 (52.6%; p = 0.024) asymptomatic intestinal parasite infected community controls (IPCC). Endo-limax nana (40%) and Entamoeba coli (22%), were the most nonpathogenic protozoan identified and Entamoeba histolytica, Giardia intestinalis, Ascaris lumbricoides and Strongyloides stercoralis were the pathogenic species (40%). IgE was higher in IPCC (p = 0.036). Cytokine profiles were significantly biased toward a Th2 type IL-5 (p = 0.001) and IL-13 (p = 0.033), pro-inflammatory GM-CSF (p = 0.019) and borderline lower IL-1β in IPTB, all associated with ESAT-6/CFP-10, while IL-7 was borderline lower, but 38 kDa/CFP-10 associated; as well as IL-8 higher (p < 0.049) vs CC/IPCC. The TB/IPTB IFN-γ levels were similar to both antigens stimuli (p ≥ 0.208). Conclusion: Therefore, coin-cident IPTB coinfection did not exert a significant inhibitory effect in IFN-γ production in response to either of the two antigens, but the partial discrepancy in Th1/Th2 response, is associated with the antigen priming cells.
Cite this paper: Silva, R. , Mello, F. , Leung, J. , Moraes Neto, A. , Fonseca, L. , Siqueira, H. , CSEGSF Team, H. and Féres Saad, M. (2018) Insights on Blood Cytokines Production under Different In Vitro Mycobacterial Antigens in Tuberculosis Intestinal Parasites Co Infected Patients. Advances in Microbiology, 8, 161-174. doi: 10.4236/aim.2018.83011.

[1]   Raja, A. (2004) Immunology of Tuberculosis. Indian Journal of Medical Research, 120, 213-232.

[2]   Hotez, P.J., Brindley, P.J., Bethony, J.M., King, C.H., Pearce, E.J. and Jacobson, J. (2008) Helminth Infections: The Great Neglected Tropical Diseases. Journal of Clinical Investigation, 118, 1311-1321.

[3]   Li, X. and Zhou, X. (2013) Co-infection of Tuberculosis and Parasitic Diseases in Humans: A Systematic Review. Parasites & Vectors, 6.

[4]   Borkow, G., Leng, Q., Weisman, Z., Stein, M., Galai, N., Kalinkovich, A. and Bentwich, Z. (2000) Chronic Immune Activation Associated with Intestinal Helminth Infections Results in Impaired Signal Transduction and Anergy. Journal of Clinical Investigation, 106, 1053-1060.

[5]   Elias, D., Wolday, D., Akuffo, H., Petros, B., Bronner, U. and Britton, S. (2001) Effect of Deworming on Human T Cell Responses to Mycobacterial Antigens in Helminth-Exposed Individuals before and after Bacille Calmette±GueArin (BCG) Vaccination. Clinical & Experimental Immunology, 123, 219-225.

[6]   Resende Co, T., Hirsch, C.S., Toossi, Z., Dietze, R. and Ribeiro-Rodrigues, R. (2007) Intestinal Helminth Co-Infection Has a Negative Impact on Both Anti-Mycobacterium tuberculosis Immunity and Clinical Response to Tuberculosis Therapy. Clinical and Experimental Immunology, 147, 45-52.

[7]   Mendez-Samperio, P. (2012) Immunological Mechanisms by Which Concomitant Helminth Infections Predispose to the Development of Human Tuberculosis. The Korean Journal of Parasitology, 50, 281-286.

[8]   Elias, D., Britton, S., Kassu, A. and Akuffo, H. (2007) Chronic Helminth Infections May Negatively Influence Immunity against Tuberculosis and Other Diseases of Public Health Importance. Expert Review of Anti-Infective Therapy, 5, 475-484.

[9]   Babu, S., Bhat, S., Kumar, N., Jayantasri, S., Rukmani, S., Kumaran, P., Gopi, P., Kolappan, C., Kumaraswami, V. and Nutman, T. (2009) Human Type 1 and 17 Responses in Latent Tuberculosis Are Modulated by Coincident Filarial Infection through Cytotoxic T lymphocyte Antigen-4 and Programmed Death-1. The Journal of Infectious Diseases, 200, 288-298.

[10]   Diniz, L., Magalhães, E.F.L., Dietze, R., Pereira, F.E.L. and Ribeiro-Rodrigues, R. (2010) Presence of Intestinal Helminths Decreases T Helper Type 1 Responses in tuberculoid Leprosy Patients and May Increase the Risk for Multi-Bacillary Leprosy. Clinical & Experimental Immunology, 161, 142-150.

[11]   Rafi, W., Ribeiro-Rodrigues, R., Ellner, J. and Salgame, P. (2012) Coinfection-Helminthes and Tuberculosis. Current Opinion in HIV and AIDS, 7, 239-244.

[12]   Bazzone, L., Smith, P., Rutitzky, L., Shainheit, M., Urban, J., Setiawan, T., Blum, A., Weinstock, J. and Stadecker, M. (2008) Coinfection with the Intestinal Nematode Heligmosomoides polygyrus Markedly Reduces Hepatic Egg-Induced Immunopathology and Proinflammatory Cytokines in Mouse Models of Severe Schistosomiasis. Infection and Immunity, 76, 5164-5172.

[13]   Belkaid, Y., Piccirillo, C., Mendez, S., Shevach, E.M. and Sacks, D.L. (2002) CD4+CD25+ Regulatory T Cells Control Leishmania major Persistence and Immunity. Nature, 420, 502-507.

[14]   Elias, D., Akuffo, H. and Britton, S. (2005) PPD Induced In Vitro Interferon Gamma Production Is Not a Reliable Correlate of Protection against Mycobacterium tuberculosis. Transactions of the Royal Society of Tropical Medicine and Hygiene, 99, 363-368.

[15]   Abbas, A., Murphy, K. and Sher, A. (1996) Functional Diversity of Helper T Lymphocytes. Nature, 383, 787-793.

[16]   Erb, K., Trujillo, C., Fugate, M. and Moll, H. (2002) Infection with the Helminth Nippostrongylus brasiliensis Does Not Interfere with Efficient Elimination of Mycobacterium bovis BCG from the Lungs of Mice. Clinical and Diagnostic Laboratory Immunology, 9, 727-730.

[17]   Frantz, F., Rosada, R., Turato, W., Peres, C., Coelho-Castelo, A., Ramos, S., Aronoff, D., Silva, C. and Faccioli, L. (2007) The Immune Response to Toxocariasis Does Not Modify Susceptibility to Mycobacterium tuberculosis Infection in BALB/c Mice. The American Journal of Tropical Medicine and Hygiene, 77, 691-698.

[18]   Tavares, R., Salgado, J., Moreira, V., Ferreira, M., Melo, F., Leung, J., Fonseca, L., Spallek, R., Singh, M. and Saad, M. (2007) Interferon Gamma Response to Combinations 38 kDa/CFP-10, 38 kDa/MPT-64, ESAT-6/MPT-64 and ESAT-6/CFP-10, Each Related to a Single Recombinant Protein of Mycobacterium tuberculosis in Individuals from Tuberculosis Endemic Areas. Microbiology and Immunology, 51, 289-296.

[19]   Diel, R., Loddenkemper, R. and Nienhaus, A. (2012) Predictive Value of Interferon-γ Release Assays and Tuberculin Skin Testing for Progression from Latent TB Infection to Disease State: A meta-analysis. Chest, 142, 63-75.

[20]   Araujo, L.S., Mello, F.Q., Silva, N.B.M., Leung, J.A.W., Machado, S.M.A., Sardella, I.G., Maciel, R.M. and Saad, M.H.F. (2014) Evaluation of Gamma Interferon Immune Response Elicited by the Newly Constructed PstS-1(285-374):CFP10 Fusion Protein to Detect Mycobacterium tuberculosis Infection. Clinical and Vaccine Immunology, 21, 552-560.

[21]   WHO (2013) Global Tuberculosis Report 2013. World Health Organization, Geneva, 289.

[22]   Lutz, A.V. (1919) O Schistosoma mansoni e Schistosomose, segundo observaçöes, feitas no Brasil. Memórias do Instituto Oswaldo Cruz, 11, 121-25.

[23]   Trist?o-Sá, R., Ribeiro-Rodrigues, R., Johnson, L., Pereira, F.E.L. and Dietze, L. (2002) Intestinal Nematodes and Pulmonary Tuberculosis. Revista da Sociedade Brasileira de Medicina Tropical, 35, 533-535.

[24]   Elias, D., Mengistu, G., Akuffo, H. and Britton, S. (2006) Are Intestinal Helminths Risk Factors for Developing Active Tuberculosis? Tropical Medicine and International Health, 11, 551-558.

[25]   Brown, M., Miiro, G., Nkurunziza, P., Watera, C., Quigley, M., Dunne, D., Whitworth, J. and Elliott, A. (2006) Schistosoma mansoni, Nematode Infections, and Progression to Active Tuberculosis among HIV-1-Infected Ugandans. The American Journal of Tropical Medicine and Hygiene, 74, 819-825.

[26]   Moraes Neto, A.H., Pereira, A.P., Alencar, M.F., Souza Jr., P.R., Dias, R.C., Fonseca, J.G., Santos, C.P. and Almeida, J.C. (2010) Prevalence of Intestinal Parasites versus Knowledge, Attitudes, and Practices of Inhabitants of Low-Income Communities of Campos dos Goytacazes, Rio de Janeiro State, Brazil. Parasitology Research, 107, 295-307.

[27]   Du Plessis, N., Kleynhans, L., Thiart, L., Van Helden, P., Brombacher, F., Horsnell, W. and Walzl, G. (2013) Acute Helminth Infection Enhances Early Macrophage Mediated Control of Mycobacterial Infection. Mucosal Immunology, 6, 931-941.

[28]   Wang, L., Cao, Y. and Shi, H.N. (2008) Helminth Infections and Intestinal Inflammation. World Journal of Gastroenterology, 14, 5125-5132.

[29]   Adams, J., Scholvinck, E., Gie, R., Potter, P., Beyers, N. and Beyers, A. (1999) Decline in Total Serum IgE after Treatment for Tuberculosis. Lancet, 353, 2030-2033.

[30]   Waitt, C.J., Peter, K.B.N., White, S.A., Kampmann, B., Kumwenda, J., Heyderman, R.S., Pirmohamed, M. and Squire, S.B. (2011) Early Deaths during Tuberculosis Treatment Are Associated with Depressed Innate Responses, Bacterial Infection, and tuberculosis Progression. The Journal of Infectious Diseases, 204, 358-362.

[31]   Waitt, C.J., Banda, P., Glennie, S., Kampmann, B., Squire, S.B., Pirmohamed, M. and Heyderman, R.S. (2015) Monocyte Unresponsiveness and Impaired IL1β, TNFα and IL7 Production Are Associated with a Poor Outcome in Malawian Adults with Pulmonary Tuberculosis. BMC Infectious Diseases, 15, 513.

[32]   Feske, M., Nudelman, R., Medina, M., Lew, J., Singh, M., Couturier, J., Graviss, E. and Lewis, D. (2008) Enhancement of Human Antigen-Specific Memory T-Cell Responses by Interleukin-7 May Improve Accuracy in Diagnosing Tuberculosis. Clinical and Vaccine Immunology, 15, 1616-1622.

[33]   Santiago, E., Mora, L., Bautista, M., Montesinos, J.J., Martinez, I., Ramos, G., Zambrano, I.R., Manrique, B. and Weiss-Steider, B. (2001) Granulocyte Colony-Stimulating Factor Induces Neutrophils to Secrete Macrophage Colony-Stimulating Factor. Cytokine, 15, 299-304.

[34]   Boneberg, E. and Hartung, T. (2002) Molecular Aspects of Anti-Inflammatory Action of G-CSF. Inflammation Research, 51, 119-128.

[35]   Rook, G.A. (2007) Th2 Cytokines in Susceptibility to Tuberculosis. Current Molecular Medicine, 7, 327-337.