Myeloid-derived suppressor cells and their importance in diseases caused by larval stages of tapeworms
Terézia Mačák Kubašková 1
Gabriela Hrčková 1
Dagmar Mudroňová 2
1 Institute of Parasitology, Slovak Academy of Sciences, Hlinkova 3, Košice, Slovak Republic 2 Institute of Microbiology and Immunology, University of Veterinary Medicine and Pharmacy in Košice, Komenského 73, Košice, Slovak Republic
|Section:||Cellular metabolism, physiology, molecular biology and genetics|
Myeloid-derived suppressor cells (MDSCs) are heterogeneous population of precursors and immature cells in different stages of differentiation. One of the typical characteristics of these cells is the regulation of adaptive immune response or the suppression of protective immune reaction and effector cells. They are also present in healthy individuals, but these cells rapidly turn into mature myeloid cells and lose the ability to inhibit effector mechanisms in hosts’ defense. Currently, suppressive influence of MDSCs is mainly examined in different cancer diseases. However, the role of MDSCs during parasitic infections is not fully reviewed. In mice, the population of immature myeloid cells is broadly characterized by the surface expression of CD11b and Gr1 molecules.
The aim of this study was to consistently characterize the different populations of myeloid cells and define their effector function in the course of larval cestodiasis, such as the production of nitric oxide in peritoneal cavity of mice infected with larval stages of Mesocestoides vogae (M. vogae). By using a mouse model of larval cestodiasis, we found that the induction of the disease was associated with infiltration of large numbers of myeloid cells into the peritoneal cavity and into the spleen of mice. We found that the population of CD11b+Gr-1+ myeloid cells (macrophages, dendritic cells, neutrophils and eosinophils) expanded gradually in the course of M. vogae infection. Moreover, flow cytometry analysis also showed that the majority of the population CD11bhighGr-1high myeloid cells express low levels of F4/80 and MHC class II molecules.
Since the population of myeloid cells possesses an ability to produce large amounts of proinflammatory mediators and nitrogen metabolites, we have analyzed nitric oxide (NO) production by peritoneal exudate cells. The gradual reduction of the NO level during the infection indicates that the population of myeloid cells in peritoneal cavity loses the characteristics of classically activated myeloid cells. Subsequently, by in vitro additional experiments, we also detected that after the M. vogae infection, the levels of IFN-γ in the supernatant of concanavalin stimulated spleen cells and the proliferation of these cells was gradually reduced. This indicates that the population of immature myeloid cells may contribute to the suppression of immune response and inhibition of effector mechanisms in hosts’ defense and represents a promising target for immunotherapy.