An immune-modulating diet increases the regulatory T cells and reduces T helper 1 inflammatory response in Leishmaniosis affected dogs treated with standard therapy.

BACKGROUND: Clinical appearance and evolution of Canine Leishmaniosis (CL) are the consequence of complex interactions between the parasite and the genetic and immunological backgrounds. We investigated the effect of an immune-modulating diet in CL. Dogs were treated with anti- Leishmania pharmacological therapy combined with standard diet (SD Group) or with the immune-modulating diet (IMMD Group). CD3+ CD4+ Foxp3+ Regulatory T cells (Treg) and CD3+ CD4+ IFN-γ + T helper 1 (Th1) were analyzed by flow cytometry. RESULTS: All sick dogs showed low platelet number at diagnosis (T0). A platelet increase was observed after six months (T6) SD Group, with still remaining in the normal range at twelve months (T12). IMMD Group showed an increase in platelet number becoming similar to healthy dogs at T6 and T12. An increase of CD4/CD8 ratio was revealed in SD Group after three months (T3), while at T6 and at T12 the values resembled to T0. The increase in CD4/CD8 ratio at T3 was maintained at T6 and T12 in IMMD Group. A reduction in the percentage of Treg of all sick dogs was observed at T0. A recovery of Treg percentage was observed only at T3 in SD Group, while this effect disappeared at T6 and T12. In contrast, Treg percentage became similar to healthy animals in IMDD Group at T3, T6 and T12. Sick dogs showed an increase of Th1 cells at T0 as compared with healthy dogs. We observed the occurrence of a decrease of Th1 cells from T3 to T12 in SD Group, although a trend of increase was observed at T6 and T12. At variance, IMMD Group dogs showed a progressive decrease of Th1 cells, whose levels became similar to healthy controls at T6 and T12. CONCLUSION: The immune-modulating diet appears to regulate the immune response in CL during the standard pharmacological treatment. The presence of nutraceuticals in the diet correlates with the decrease of Th1 cells and with the increase of Treg in sick dogs. Therefore, the administration of the specific dietary supplement improved the clinical response to the standard treatment in a model of CL.

Regulatory T cells, Cytotoxic T lymphocytes and a T(H)1 cytokine profile in dogs naturally infected by Leishmania infantum.

Canine leishmaniasis caused by the protozoan parasite Leishmania infantum is a chronic systemic disease endemic in Mediterranean basin. The aim of the study is to investigate the immune profile of dogs naturally infected by Leishmania infantum. In order to address such issue, CD4(+) and CD8(+) lymphocyte T cell subsets, peripheral CD4(+)CD3(+)Foxp3(+) (Treg) levels and the presence of pro-inflammatory T cells have been assessed, in 45 infected dogs and in 30 healthy animals, by using immunofluorescence and flow cytometry detection. Animals were categorised according to their clinical-pathological status and their antibody titer at diagnosis. Results showing a significant increase of CD8(+)CD3(+) T lymphocytes, a reduced percentage of the T regulatory CD4(+)CD3(+)Foxp3(+) subset and a significant increase of T(H)1 cells, characterise the infected dogs, regardless of their antibody titer or the occurrence of clinical symptomatic disease. These data may provide new insights into the pathogenesis of immune-mediated alterations associated with canine leishmaniasis.

Natural killer expansion, human leukocyte antigens-E expression and CD14(+) CD56(+) monocytes in a myelodysplastic syndrome patient.

Myelodysplastic syndromes (MDS) are clonal disorders characterized by ineffective hematopoiesis and possible evolution to acute leukemia. Occurrence of stem cell defects and of immune-mediated mechanisms was evidenced as relevant for pathophysiology of MDS. Here, we described one case of MDS patient carrying CD14(+) CD56(+) monocytes in bone marrow (BM), in the presence of a defective human leukocyte antigen (HLA)-E expression on peripheral blood (PB) cells and of natural killer (NK) cell expansion in PB and BM. The defective HLA-E expression and the NK expansion are proposed to be relevant for the pathogenesis of myelodysplasia in those patients showing CD14(+) CD56(+) monocytes in BM.

Eculizumab treatment modifies the immune profile of PNH patients.

Paroxysmal Nocturnal Haemoglobinuria (PNH) is due to pathological expansion of a stem progenitor bearing a somatic mutation of PIG-A gene involved in the biosynthesis of the glycosyl-phosphatidyl-inositol (GPI) anchor. Numerous data suggest a role for immune-mediated mechanisms in the selection/expansion of GPI-defective clone. Haemolytic anaemia in PNH is dependent on the effect of complement against GPI-defective red cells. Eculizumab, an anti-C5 monoclonal antibody, is dramatically effective in controlling haemolysis and thrombosis, in reducing fatigue and in improving quality of life of patients. However, this therapy presents new challenges that need to be properly faced. Here, we report the decrease in B, Natural Killer (NK) and regulatory T cells (Treg), an altered cytokine profile of invariant-NKT cells (NKTi) and the increasing of C-X-C chemokine receptor type 4 (CXCR4) receptor in PNH patients before the Eculizumab therapy. Treatment significantly affects some of these alterations: after Eculizumab, the number of B lymphocytes, the cytokine secretion of NKTi and CXCR4 expression on CD8 T cells became similar to healthy donors. No effects were observed on NK and Treg. The amplitude of the GPI-defective compartment remained unchanged.