S. Warren, J. Barragan, S.Y. Lee, R. Siddiqui, A Serizawa, and J. Cervantes
Texas Tech University Health Sciences Center,
United States
Keywords: TiO2, nanoparticles, leprosy
Summary:
Introduction. Leprosy is a chronic infectious disease caused by Mycobacterium leprae, which is still endemic in many parts of the world including Southern Texas. The two polar clinical forms of leprosy, termed tuberculoid and lepromatous, have polarized cellular immune responses, with complex immunological distinctions. Dendritic cells (DCs) are the primary antigen presenting cells in the immune system. TiO2 nanoparticles have shown to induce maturation of these cells leading to an inflammatory response. Objective. We aimed to evaluate the effect of potassium incorporated TiO2 nanostructures, namely KTiOx, in the response of human monocyte-derived-DCs to M. leprae. Methodology: THP-1 human monocytes were differentiated and maturated into DCs using commercially available media, and then treated with KTiOx for 24 hours. Following, cells were infected with M.leprae at an MOI of 10:1 for 24 hours. Secreted human cytokines were measured in the culture supernatants by a multiplex ELISA system. Results: We observed an increase in the levels of secreted IFN- and TNF- upon M. leprae infection in cells treated with KTiOx. IFN-β and its downstream gene IL-10 are preferentially expressed in disseminated and progressive lepromatous lesions, while TNF-β gene is identified as a major risk factor for early-onset leprosy. Interestingly, the levels of cytokine secretion differ comparing 1 M KOH treated Ti and 10 M KOH treated Ti. This can be explained by a wider surface area of the 10M preparation compared to 1 M KOH treated Ti. It is possible that this wider KTiOx area can activate more DCs due to an increase in the contact area. Conclusion: This study demonstrates the effect of nanostructures of KTiOx and the usefulness of nanoparticle technology in the in vitro activation of human DCs against an infectious disease with a puzzling immune spectrum. Our findings may prompt future therapeutic strategies such as DC immunotherapy for disseminated and progressive lepromatous lesions.