Soluble CD40 Ligand in Sera of Subjects Exposed to Leishmania infantum Infection Reduces the Parasite Load in Macrophages

• Published in: PloS one Vol. 10; no. 10; p. e0141265
• Main Authors: Oliveira, Fabrícia Alvisi de, Barreto, Aline Silva, Bomfim, Lays G. S., Leite, Talita Rebeca S., dos Santos, Priscila Lima, Almeida, Roque Pacheco de, Silva, Ângela Maria da, Duthie, Malcolm S., Reed, Steven G., de Moura, Tatiana Rodrigues, Ribeiro de Jesus, Amélia
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 21.10.2015; Public Library of Science (PLoS)
• Subjects: Antibodies, Monoclonal - immunology; Antigen-presenting cells; Antigens; Antigens, Protozoan - immunology; Bacterial infections; Biological activity; Care and treatment; CD40 antigen; CD40 Ligand - blood; CD40 Ligand - immunology; CD40L protein; Cell culture; Cytokines; Dendritic cells; Exposure; Gene expression; Genetic aspects; Glycoprotein; Glycoproteins; Humans; Immune response; Infections; Infectious diseases; Interleukin 1; Interleukin 12; Interleukin 15; Interleukin 23; Interleukin 27; Interleukins - immunology; Intracellular; Leishmania infantum; Leishmania infantum - immunology; Leishmaniasis; Leishmaniasis, Visceral - blood; Leishmaniasis, Visceral - immunology; Leishmaniasis, Visceral - parasitology; Ligands; Lymphocyte Activation - immunology; Lymphocytes; Lymphocytes T; Macrophages; Macrophages - immunology; Macrophages - parasitology; Monoclonal antibodies; Parasite control; Parasite Load - methods; Parasites; Parasitic diseases; Platelets; Promastigotes; Properties; R&D; Recombinant; Research & development; Rodents; Vector-borne diseases; Visceral leishmaniasis; Brazil; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0141265

While CD40L is typically a membrane glycoprotein expressed on activated T cells and platelets that binds and activates CD40 on the surface on antigen presenting cells, a soluble derivative (sCD40L) that appears to retain its biological activity after cleavage from cell membrane also exists. We recently reported that sCD40L is associated with clinical resolution of visceral leishmaniasis and protection against the disease. In the present study we investigated if this sCD40L is functional and exerts anti-parasitic effect in L. infantum-infected macrophages. Macrophages from normal human donors were infected with L. infantum promastigotes and incubated with either sera from subjects exposed to L. infantum infection, monoclonal antibodies against human CD40L, or an isotype control antibody. We then evaluated infection by counting the number of infected cells and the number of parasites in each cell. We also measured a variety of immune modulatory cytokines in these macrophage culture supernatants by Luminex assay. The addition of sCD40L, either recombinant or from infected individuals' serum, decreased both the number of infected macrophages and number of intracellular parasites. Moreover, this treatment increased the production of IL-12, IL-23, IL-27, IL-15, and IL1β such that negative correlations between the levels of these cytokines with both the infection ratio and number of intracellular parasites were observed. sCD40L from sera of subjects exposed to L. infantum is functional and improves both the control of parasite and production of inflamatory cytokines of infected macrophages. Although the mechanisms involved in parasite killing are still unclear and require further exploration, these findings indicate a protective role of sCD40L in visceral leishmaniasis.