A New Vaccine Strategy of Dendritic Cell Presented Kinetoplastid Membrane (KMP-11) as Immunogen for Control against Experimental Visceral Leishmaniasis
Available reports suggest that, Leishmania donovani antigen KMP-11 may
be significant in the modulation of immune responses in visceral leishmaniasis (VL).
This study evaluated vaccine prospect of presentation of KMP-11 antigen through
murine dendritic cells against VL in infected BALB/c mice. We report here that immunization
with KMP-11 delivered through bone marrow derived dendritic cells can lead to killing
of L. donovani in infected BALB/c mice.
Furthermore, the strategy to use KMP-11 as vaccine delivered through DCs can stimulate
the production of IFN-g, IL-12, IL-2R and TNF-α with
concomitant down-regulation of IL-10 and IL-4. Furthermore, anti-leishmanial defence function (ROS) of splenocytes was observed increased in the presence
of DC-delivered KMP-11 vaccination accompanied with an increased p38-MAPK signalling
in vaccinated splenocytes. We summarized from our data that
KMP-11 delivered through DCs has potential for eliciting protective immunity through
pro-inflammatory cytokines (IFN-γ, IL-12, IL-2, TNF-α) following an up-regulation
in signalling event of p38-MAPK. Therefore the study suggests a new control strategy
against VL in future.
References
[1]
Desjeux, P. (1992) Human Leishmaniases: Epidemiology and Public Health Aspects. World Health Statistics Quarterly, 45, 267-275.
[2]
Croft, S.L., Sundar, S., and Fairlamb, A.H. (2006) Drug Resistance in Leishmaniasis. Clinical Microbiology Reviews, 19, 111-126. https://doi.org/10.1128/CMR.19.1.111-126.2006
[3]
Basu, J.M., Mookerjee, A., Banerjee, R., Saha, M., Singh, S., Naskar, K., Tripathy, G., Sinha, P.K., Pandey, K., Sundar, S., Bimal, S., Das, P.K., Choudhuri, S.K. and Roy, S. (2008) Inhibition of ABC Transporters Abolishes Antimony Resistance in Leishmania Infection. Antimicrobial Agents and Chemotherapy, 52, 1080-1093. https://doi.org/10.1128/AAC.01196-07
[4]
Singh, O.P. and Sundar, S. (2015) Development in Diagnosis of Visceral Leishmaniasis in the Elimination Era. Journal of Parasitology Research (Hindawi), 2015, Article ID: 239469.
[5]
Scott, P. and Hunter, C.A. (2002) Dendritic Cells and Immunity to Leishmaniasis and Toxoplasmosis. Current Opinion in Immunology, 14, 466-470. https://doi.org/10.1016/S0952-7915(02)00353-9
[6]
Ghosh, M. and Bandhopadhyay, S. (2004) Interaction of Leishmania Parasites with Dendritic Cells and Its Functional Consequences. Immunobiology, 209, 173-177. https://doi.org/10.1016/j.imbio.2004.02.007
[7]
Hart, D.N.J. (1997) Dendritic Cells: Unique Leukocyte Populations Which Control the Primary Immune Response. Blood, 90, 3245-3287.
[8]
Carrera, L., Gazzinelli, R.T., Badolato, R. et al. (1996) Leishmania Promastigotes Selectively Inhibit Interleukin 12 Induction in Bone Marrow-Derived Macrophages from Susceptible and Resistant Mice. Journal of Experimental Medicine, 183, 515-526. https://doi.org/10.1084/jem.183.2.515
[9]
Sartori, A., Oliveira, M.A.P., Scott, P. and Trinchieri, G. (1997) Metacyclogenesis Modulates the Ability of Leishmania Promastigotes to Induce IL-12 Production in Human Mononuclear Cells. Journal of Immunology, 159, 2849-2857.
[10]
Beverley, S.M. and Turco, S.J. (1998) Lipophosphoglycan (LPG) and the Identification of Virulence Genes in the Protozoan Parasite Leishmania. Trends in Microbiology, 6, 35-40. https://doi.org/10.1016/S0966-842X(97)01180-3
[11]
Jardim, A., Funk, V., Caprioli, R.M. and Olafson, R.W. (1995) Isolation and Structural Characterization of the Leishmania donovani Kinetoplastid Membrane Protein-11, a Major Immunoreactive Membrane Glycoprotein. Biochemical Journal, 305, 307-313. https://doi.org/10.1042/bj3050307
[12]
Basu, R., Bhaumik, S., Basu, J.M., Naskar, K., De, T. and Roy, S. (2005) Kinetoplastid Membrane Protein-11 DNA Vaccination Induces Complete Protection against Both Pentavalent Antimonial-Sensitive and Resistant Strains of Leishmania donovani That Correlates with Inducible Nitric Oxide Synthase Activity and IL-4 Generation: Evidence for Mixed Th1- and Th2-Like Responses in Visceral Leishmaniasis. The Journal of Immunology, 174, 7160-7171. https://doi.org/10.4049/jimmunol.174.11.7160
[13]
Kurtzhals, J.A.L., Hey, A.S., Jardim, A., et al. (1994) Dichotomy of the Human T Cell Response to Leishmania Antigens. II. Absent of Th2-Like Response to gp63 and Th1-Like Response to Lipophosphoglycan-Associated Protein in Cells from Cured Visceral Leishmaniasis Patients. Clinical and Experimental Immunology, 96, 416-421. https://doi.org/10.1111/j.1365-2249.1994.tb06044.x
[14]
Chaudhary, R., Amit, A., Yadav, A., Singh, A., Kumar, V., Singh, S.K., Narayan, S., Das, V.N.R., Pandey, K., Kumar, A., Das, P. and Bimal, S. (2014) Immunomodulation in Human Dendritic Cells Leads to Induction of Interferon-Gamma Production by Leishmania donovani Derived KMP-11 Antigen via Activation of NF-κB in Indian kala-azar Patients. Biomed Research International, 2014, Article ID: 947606.
[15]
Inaba, K., Inaba, M., Romani, N., Aya, H., Deguchi, M., et al. (1992) Generation of Large Numbers of Dendritic Cells from Mouse Bone Marrow Cultures Supplemented with Granulocyte/Macrophage Colony-Stimulating Factor. The Journal of Experimental Medicine, 176, 1693-1702. https://doi.org/10.1084/jem.176.6.1693
[16]
Singh, S.K., Bimal, S., Narayan, S., Jee, C., Bimal, D., Das, P. and Bimal, R. (2010) Leishmania donovani: Assessment of Leishmanicidal Effects of Herbal Extracts Obtained from Plants in the Visceral Leishmaniasis Endemic Area of Bihar, India. Experimental Parasitology, 127, 552-558.
[17]
Lamelli, U.K. (1970) Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4. Nature, 227, 680-685. https://doi.org/10.1038/227680a0
[18]
Salotra, P., Raina, A. and Ramesh, V. (1999) Western Blot Analysis of Humoral Immune Response to Leishmania donovani Antigens in Patients with Post-Kala-Azar Dermal Leishmaniasis. Transactions of the Royal Society of Tropical Medicine and Hygiene, 93, 98-101.
[19]
Mukhopadhyay, A., Chaudhuri, G., Arora, S.K., Sehgal, S. and Basu, S.K. (1989) Receptor-Mediated Drug Delivery to Macrophages in Chemotherapy of Leishmaniasis. Science, 244, 705-707. https://doi.org/10.1126/science.2717947
[20]
Stager, S., Smith, D.F. and Kaye, P.M. (2000) Immunization with a Recombinant Stage-Regulated Surface Protein from Leishmania donovani Induces Protection against Visceral Leishmaniasis. The Journal of Immunology, 165, 7064-7071. https://doi.org/10.4049/jimmunol.165.12.7064
[21]
Prussin, C. and Metcalfe, D.D. (1995) Detection of Intracytoplasmic Cytokine Using Flow Cytometry and Directly Conjugated Anticytokine Antibodies. Journal of Immunological Methods, 188, 117-128.
[22]
Mukhopadhyay, S., Sen, P., Majumder, H.K. and Roy, S. (1998) Reduced Expression of Lipophosphoglycan (LPG) and Kinetoplastid Membrane Protein (KMP)-11 in Leishmania donovani Promastigotes in Axenic Culture. The Journal of Parasitology, 84, 644-647. https://doi.org/10.2307/3284745
[23]
Naderer, T., Vince, J.E. and McConville, M.J. (2004) Surface Determinants of Leishmania Parasites and Their Role in Infectivity in the Mammalian Host. Current Molecular Medicine, 4, 649-665. https://doi.org/10.2174/1566524043360069
[24]
Basu, R., Roy, S. and Walden, P. (2007) HLA Class I—Restricted T-Cell Epitopes of the Kinetoplastid Membrane Protein-11 Presented by Leishmania donovani Infected Human Macrophages. The Journal of Infectious Diseases, 195, 1373-1380. https://doi.org/10.1086/513439
[25]
Stenger, S., Niazi, K.R. and Modlin, R.L. (1998) Down-Regulation of CD1 on Antigen-Presenting Cells by Infection with Mycobacterium Tuberculosis. The Journal of Immunology, 161, 3582-3588.
[26]
Adhikari, A., Gupta, G., Majumdar, S., Banerjee, S., Bhattarcharjee, S., Bhattachary, P., Kumari, S., Haldar, S., Majumdar, S.B., Saha, B. and Majumdar, S. (2012) Mycobacterium Indicus Pranii (Mw) Re-Establishes Host Protective Immune Response in Leishmania donovani Infected Macrophages: Critical Role of IL-12. PLoS ONE, 7, e40265. https://doi.org/10.1371/journal.pone.0040265
[27]
Zaph, C. and Scott, P. (2003) Interleukin-12 Regulates Chemokine Gene Expression during Early Immune Response to Leishmania Major. Infection and Immunity, 7, 1587-1589. https://doi.org/10.1128/IAI.71.3.1587-1589.2003
[28]
Padigel, U.M., Kim, N., Choi, Y. and Farrell, J.P. (2003) Trance-Rank Costimulation Is Required for IL-12 Production and the Initiation of a Th1-Type Response to Leishmania Major Infection in CD40L-Deficient Mice. The Journal of Immunology, 171, 5437-5441. https://doi.org/10.4049/jimmunol.171.10.5437
[29]
Jones, D.E., Ackermann, M.R., Wille, U., Hunter, C.A. and Scott, P. (2002) Early Enhanced Th1 Response after Leishmania amazonensis Infection of C57BL/6 Interleukin-10-Deficient Mice Does Not Lead to Resolution of Infection. Infection and Immunity, 70, 2151-2158. https://doi.org/10.1128/IAI.70.4.2151-2158.2002
[30]
Diefenbach, A., Schindler, H., Rollinghoff, M., et al. (1999) Requirement for Type 2 NO Synthase for IL-12 Signaling in Innate Immunity. Science, 284, 951-955. https://doi.org/10.1126/science.284.5416.951
