CCR2 signaling contributes to the differentiation of protective inflammatory dendritic cells in Leishmania braziliensis infection

Author(s)

Costa, Diego L. ^[1] ; Lima-Junior, Djalma S. ^[1] ; Nascimento, Manuela S. ^[1] ; Sacramento, Lais A. ^[1] ; Almeida, Roque P. ^[2] ; Carregaro, Vanessa ^[1] ; Silva, Joao S. ^[1]

Affiliation

^[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Biochem & Immunol, Ave Bandeirantes 3900, BR-14049900 Ribeirao Preto, SP - Brazil

^[2] Univ Fed Sergipe, Ctr Biol & Hlth Sci, Dept Internal Med & Pathol, Aracaju, SE - Brazil

• Document type: Journal article
• Source: Journal of Leukocyte Biology; v. 100, n. 2, p. 423-432, AUG 2016.
• Web of Science Citations: 2

Abstract

In vertebrate hosts, Leishmania braziliensis parasites infect mainly mononuclear phagocytic system cells, which when activated by T helper cell type 1 cytokines produce nitric oxide and kill the pathogens. Chemokine (C-C motif) receptor 2 is a chemokine receptor that binds primarily chemokine (C-C motif) ligand 2 and has an important role in the recruitment of monocytic phagocytes. Although it has been reported that Leishmania braziliensis infection induces CCR2 expression in the lesions, the role ofCCR2 during Leishmania braziliensis infection remains unknown. Here, we showed that CCR2 has a role in mediating protection against Leishmania braziliensis infection in mice. The absence of CCR2 resulted in increased susceptibility to infection and was associated with low amounts of Ly6C(+) inflammatory dendritic cells in the lesions, which we found to be the major sources of tumor necrosis factor production and induced nitric oxide synthase expression in C57BL/6 mice lesions. Consequently, CCR22/2 mice showed decreased tumor necrosis factor production and induced nitric oxide synthase expression, resulting in impaired parasite elimination. We also demonstrated that CCR2 has a role in directly mediating the differentiation of monocytes into inflammatory dendritic cells at the infection sites, contributing to the accumulation of inflammatory dendritic cells in Leishmania braziliensis lesions and subsequent control of parasite replication. Therefore, these data provide new information on the role of chemokines during the immune response to infections and identify a potential target for therapeutic interventions in cutaneous leishmaniasis. (AU)

• FAPESP's process: 08/05982-8 - Modulation of immune responses to Leishmania braziliensis by regulatory T cells
• Grantee: Diego Luís Costa
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 07/53940-0 - The regulatory T cells and TH17 in the immune response against infections, tumors and autoimmune diseases
• Grantee: João Santana da Silva
• Support Opportunities: Research Projects - Thematic Grants