Glycyrrhizic acid-mediated subdual of myeloid-derived suppressor cells induces antileishmanial immune responses in a susceptible host.
CD11b(+) Gr1(+) myeloid-derived suppressor cells (MDSCs), a heterogeneous population of precursor cells, modulate protective immunity against visceral leishmaniasis by suppressing T cell functions. We observed that CD11b(+) Gr1(+) MDSCs, which initially expanded in soluble leishmanial antigen (SLA)-immunized mice and later diminished, suppressed proliferation of T cells isolated from SLA-immunized mice, but to a lesser extent than the case in naive mice. This lesser suppression of MDSCs accompanied the expression of F4/80 and the production of Cox-2, arginase I, nitric oxide, and PGE2. However, with SLA immunization, there was no difference in the expression of interleukin-2 (IL-2) or gamma interferon (IFN-γ) by T cells, in contrast to the case in nonimmunized mice, in which there is an influence. Glycyrrhizic acid (a triterpenoid compound)-mediated inhibition of Cox-2 in myeloid-derived suppressor cells influenced the capacity of T cells to proliferate and the expression of IL-2 and IFN-γ in Leishmania donovani-infected BALB/c mice. Further characterization confirmed that administration of glycyrrhizic acid to L. donovani-infected BALB/c mice results in an impairment of the generation of MDSCs and a reciprocal organ-specific proliferation of IFN-γ- and IL-10-expressing CD4(+) and CD8(+) T cells. Comprehensive knowledge on the Cox-2-mediated regulation of myeloid-derived suppressor cells might be involved in unlocking a new avenue for therapeutic interventions during visceral leishmaniasis.
Division of Molecular Medicine, Bose Institute, Kolkata, India.
Syamdas
S
Bandyopadhyay
Division of Molecular Medicine, Bose Institute, Kolkata, India.
Amrita
A
Bhattacharjee
Division of Molecular Medicine, Bose Institute, Kolkata, India.
Sayantan
S
Banerjee
Division of Molecular Medicine, Bose Institute, Kolkata, India.
Kuntal
K
Halder
Division of Molecular Medicine, Bose Institute, Kolkata, India.
Shibali
S
Das
Division of Molecular Medicine, Bose Institute, Kolkata, India.
Bidisha
B
Paul Chowdhury
Division of Molecular Medicine, Bose Institute, Kolkata, India subrata@jcbose.ac.in.
Subrata
S
Majumdar
D000818:Animals; D000943:Antigens, Differentiation / Q000235:genetics / Q000276:immunology; D000953:Antigens, Protozoan / Q000008:administration & dosage; D001119:Arginase / Q000235:genetics / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D049109:Cell Proliferation; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000276:immunology; D015232:Dinoprostone / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D005786:Gene Expression Regulation; D019695:Glycyrrhizic Acid / Q000494:pharmacology*; D054884:Host-Pathogen Interactions; D007114:Immunization; D007155:Immunologic Factors / Q000494:pharmacology*; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D007376:Interleukin-2 / Q000235:genetics / Q000276:immunology; D007893:Leishmania donovani / Q000187:drug effects* / Q000254:growth & development / Q000276:immunology / Q000472:pathogenicity; D007898:Leishmaniasis, Visceral / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control; D051379:Mice; D008807:Mice, Inbred BALB C; D022423:Myeloid Cells / Q000187:drug effects* / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D015398:Signal Transduction; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology / Q000382:microbiology / Q000473:pathology
D000943:Antigens, Differentiation; D000953:Antigens, Protozoan; D007155:Immunologic Factors; D007376:Interleukin-2; C036763:monocyte-macrophage differentiation antigen; D009569:Nitric Oxide; D019695:Glycyrrhizic Acid; D007371:Interferon-gamma; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; C544448:Arg1 protein, mouse; D001119:Arginase; D015232:Dinoprostone