Leishmania infantum induces high phagocytic capacity and intracellular nitric oxide production by human proinflammatory monocyte

Abstract

BACKGROUND The mechanism of resistance to Sb III in Leishmania is complex, multifactorial and involves not only biochemical mechanisms, but also other elements, such as the immune system of the host. OBJECTIVES In this study, putative changes in the immunological profile of human monocytes infected with wild-type (WT) and antimony (Sb III)-resistant Leishmania (Viannia) braziliensis and Leishmania (Leishmania) infantum lines were evaluated. METHODS Susceptibility assays WT and SbIII-resistant L. braziliensis and L. infantum were performed using lines THP-1 human monocytic lineage. Phagocytic capacity, cytokine profile, intracellular nitric oxide (NO) production and surface carbohydrate residues profile were performed in peripheral blood monocytes by flow cytometry. FINDINGS The phagocytic capacity and intracellular NO production by classical (CD14 ++ CD16-) and proinflammatory (CD14 ++ CD16 +) monocytes were higher in the presence of L. infantum lines compared to L. braziliensis lines. The results also highlight proinflammatory monocytes as the cellular subpopulation of major relevance in a phagocytosis event and NO expression. It is important to note that L. infantum induced a proinflammatory cytokine profile characterised by higher levels of TNF-α in culture supernatant than L. braziliensis. Conversely, both Leishmania lines induce high levels of IL-6 in culture supernatant. Analysis of the expression profile of surface carbohydrates showed that L. braziliensis presents 4.3-fold higher expression of galactose(β1,4)N-acetylglucosamine than L. infantum line. Interestingly, the expression level of α-N-acetylgalactosamine residues was 2-fold lower in the Sb III-resistant L. braziliensis line than its counterpart WT line, indicating differences in surface glycoconjugates between these lines. MAIN CONCLUSIONS Our results showed that L. braziliensis and L. infantum induce different innate immune responses and a highly inflammatory profile, which is characteristic of infection by L. infantum, the species associated with visceral disease.

The Jieduan-Niwan (JDNW) Formula Ameliorates Hepatocyte Apoptosis: A Study of the Inhibition of E2F1-Mediated Apoptosis Signaling Pathways in Acute-on-Chronic Liver Failure (ACLF) Using Rats

“…[51][52][53] When D-GalN and LPS reach the liver, the Kupffer cells and blood sinusoidal endothelial cells of the liver are stimulated to produce and release a large number of inflammatory factors, particularly TNFα and IL-6, which could promote the proliferation and differentiation of cytotoxic T lymphocytes, enhance the cytolytic function of Natural Killer (NK) cells against physiologically stressed cells, provoke cellular immunity, and cause different degrees of inflammatory response and immune damage. [54][55][56][57] TNF-α binds to TNFR1 forms an oligomer, which could transmit the signals activated by the extracellular TNF-α to the cell, regulates tyrosine phosphorylation and the expression of E2F1 through the signal transducer and activator of transcription 3 (STAT3), 9 and then produces a series of molecular events. Our previous experimental studies found that the serum and liver tissues of ACLF rats showed increased levels of TNF-α and IL-6; the opposite effects were observed in the JDNW formula groups, with the most significant difference found mainly on the 15th day.…”

The Multiple Faces of Nitric Oxide in Chronic Granulomatous Disease: A Comprehensive Update

“…Today, the microbicidal capacity of NO is well known [ 50 , 51 ] and many pathogens have developed immune response evasion mechanisms based on the inhibition of NO generation [ 52 ]. Thus, therapies based on NO-releasing agents are currently being developed to treat aggressive infections in humans [ 53 ].…”

Determinants of Innate Immunity in Visceral Leishmaniasis and Their Implication in Vaccine Development

“…A growing body of research is focused on elucidating the role of sub-populations of monocytes such as iMOs, intermediate, and non-classical patrolling monocytes in Leishmania infection. Monocytic subsets (CD14+ CD16- and CD14+ CD16+) of human origin displayed significantly increased phagocytic capacity and intracellular NO production when infected with L. infantum , compared to L. braziliensis ( 77 ). iMOs contribute to parasite control at the lesion site in CL ( 78 ), but they play a detrimental role in VL ( 59 ).…”