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. 2018 Jan:93:173-183.
doi: 10.1016/j.molimm.2017.11.018. Epub 2017 Nov 29.

Susceptibility of dendritic cells from individuals with schistosomiasis to infection by Leishmania braziliensis

Diego Mota Lopes  1 , Tarcísio Vila Verde S de Almeida  2 , Robson da Paixão de Souza  3 , Luís Eduardo Viana Ribeiro  3 , Brady Page  4 , Jamille de Souza Fernandes  5 , Edgar M Carvalho  6 , Luciana Santos Cardoso  7
Affiliations

Susceptibility of dendritic cells from individuals with schistosomiasis to infection by Leishmania braziliensis

Diego Mota Lopes et al. Mol Immunol. 2018 Jan.

Abstract

Coinfection with leishmaniasis and schistosomiasis has been associated with increased time to healing of cutaneous lesions of leishmaniasis. The objective of this study was to evaluate the effect of Leishmania braziliensis infection on co-cultures of monocyte-derived dendritic cells (MoDCs) with autologous lymphocytes from patients with schistosomiasis and patients with cutaneous leishmaniasis. MoDCs were differentiated from peripheral blood monocytes, isolated by magnetic beads, infected with L. braziliensis, and co-cultured with autologous lymphocytes. Expression of HLA-DR, CD1a, CD83, CD80, CD86, CD40, and the IL-10 receptor (IL-10R) on MoDCs as well as CD28, CD40L, CD25, and CTLA-4 on lymphocytes were evaluated by flow cytometry. The production of the cytokines IL-10, TNF, IL-12p40, and IFN-γ were evaluated by sandwich ELISA of the culture supernatant. The infectivity evaluation was performed by light microscopy after concentration of cells by cytospin and Giemsa staining. It was observed that the frequency of MoDCs expressing CD83, CD80, and CD86 as well as the MFI of HLA-DR were smaller in the group of patients with schistosomiasis compared to the group of patients with leishmaniasis. On the other hand, the frequency of IL-10R on MoDCs was higher in patients with schistosomiasis than in patients with leishmaniasis. CD4+ and CD8+ T lymphocytes from patients with schistosomiasis presented a lower frequency of CD28 and a higher frequency of CTLA-4 compared to lymphocytes from patients with leishmaniasis. Levels of IL-10 were higher in the supernatants of co-cultures from individuals with schistosomiasis compared to those with leishmaniasis. However, levels of TNF, IL-12p40, and IFN-γ were lower in the group of individuals with schistosomiasis. Regarding the frequency of MoDCs infected by L. braziliensis after 72h in culture, it was observed that higher frequencies of cells from patients with schistosomiasis were infected compared to cells from patients with leishmaniasis. It was concluded that MoDCs from patients with schistosomiasis are more likely to be infected by L. braziliensis, possibly due to a lower degree of activation and a regulatory profile.

Keywords: Dendritic cells; Leishmania braziliensis; Leishmaniasis; Schistosomiasis.

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Conflict of interest statement

Disclosures

Participants in this study do not present any conflicts of interest.

Figures

Fig. 1.
Fig. 1.
(A) Selection strategy via a non-specific fluorescence densitometry plot for size (FSC) and cell granularity (SSC) to identify populations of dendritic cells and lymphocytes; (B) The marker of MoDCs (CD11c+) evaluated within the MoDC population; (C) Total T cell populations. (D) The subpopulations CD4+ and CD8+ gated within the T lymphocytes; (E) A representative gating of cell surface markers at the dendritic cells (HLA-DR, CD86, CD40, and IL-10R); (F) A A representative gating of surface cell markers at TCD4+ lymphocytes (CD28, CD40L, CD25, CTLA-4).
Fig. 2.
Fig. 2.
Frequency of activation, co-stimulatory, maturation, and regulatory molecules in MoDCs from patients with schistosomiasis and leishmaniasis infected with L. braziliensis and co-cultured with autologous lymphocytes. (A) CD11c+HLA-DR+ (MFI), (B) CD11c+CD80+ (%), (C) CD11c+CD86+ (%), (D) CD11c+CD83+ (%), (E) CD11c+CD40+ (%), and (F) CD11c+IL-10R+ (%). *p < 0.05 and **p < 0.005. Kruskal Wallis test.
Fig. 3.
Fig. 3.
Frequency of CD3+CD4+ T lymphocytes (A) expressing CD4+CD28+ co-stimulatory molecules (B), CD4+CD40L+ (C), CD4+CD25low (D), CD4+CD25high (E), and CD4+CTLA-4+ (F) after 24 h of co-culture with MoDCs infected for 2 h by L. braziliensis. *p < 0.05, **p < 0.005, and ***p < 0.001. Kruskal Wallis test.
Fig. 4.
Fig. 4.
Frequency of CD3+CD8+ T lymphocytes (A) expressing CD8+CD28+ co-stimulatory molecules (B), CD8+CD40L+ (C), CD8+CD25+ (D), and CD8+CTLA-4+ (E) after 24 h of co-culture with MoDCs infected for 2 h by L. braziliensis. *p < 0.05, **p < 0.005, and ***p < 0.001. Kruskal Wallis test.
Fig. 5.
Fig. 5.
Production of cytokines from dendritic cell cultures infected by L. braziliensis for 2 h after 24 h of co-culture with autologous lymphocytes from patients with schistosomiasis, leishmaniasis, and controls. (A) IL-10, (B) IL-12p40, (C) TNF, and (D) INF-γ. *p < 0.05, **p < 0.005, and ***p < 0.001. Kruskal Wallis test.
Fig. 6.
Fig. 6.
Kinetics of the frequency of MoDCs infected for 2 h by L. braziliensis and co-cultured with autologous lymphocytes for 24h, 48h and 72h (A). Number of intracellular amastigotes in 100 cells evaluated (B) by light microscopy (100X). ***p < 0.001. Kruskal Wallis test.
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