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BMC Infectious Diseases
Published in: BMC Infectious Diseases 1/2017

Open Access 01-12-2017 | Research article

Regulatory monocytes in helminth infections: insights from the modulation during human hookworm infection

Authors: Lívia Silva Araújo Passos, Pedro Henrique Gazzinelli-Guimarães, Tiago Antônio de Oliveira Mendes, Ana Clara Gazzinelli Guimarães, Denise da Silveira Lemos, Natasha Delaqua Ricci, Ricardo Gonçalves, Daniella Castanheira Bartholomeu, Ricardo Toshio Fujiwara, Lilian Lacerda Bueno

Published in: BMC Infectious Diseases | Issue 1/2017

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Abstract

Background

While the macrophage polarization is well characterized in helminth infections, the natural heterogeneity of monocytes with multiple cell phenotypes might influence the outcome of neglected diseases, such hookworm infection. Here, we report the profile of monocytes in human hookworm infections as a model to study the regulatory subpopulation of monocytes in helminth infections.

Methods

Blood samples were collected from 19 Necator americanus-infected individuals and 13 healthy individuals. Peripheral blood mononuclear cells (PBMCs) were isolated, and immunophenotyping was conducted by flow cytometry. The expressions of genes encoding human nitric oxide synthase (iNOS), interleukin 4 (IL-4), arginase-1 (Arg-1) and glyceraldehyde 3-phosphate dehydrogenase were quantified by qPCR. Plasma levels of IL-4 were determined by sandwich ELISA. Unpaired t-tests or Mann-Whitney tests were used depending on the data distribution.

Results

Hookworm infected individuals (HWI) showed a significant increase in the number of monocytes/mm3 (555.2 ± 191.0) compared to that of the non-infected (NI) individuals (120.4 ± 44.7) (p < 0.0001). While the frequencies of CD14+IL-10+ and CD14+IL-12+ cells were significantly reduced in the HWI compared to NI group (p = 0.0289 and p < 0.0001, respectively), the ratio between IL-10/IL-12 producing monocytes was significantly elevated in HWI (p = 0.0004), indicating the potential regulatory activity of these cells. Measurement of IL-4 levels and gene expression of IL-4 and Arg-1 (highly expressed in alternatively activated macrophages) revealed no significant differences between the NI and HWI groups. Interestingly, individuals from the HWI group had higher expression of the iNOS gene (associated with a regulatory profile) (20.27 ± 2.97) compared to the NI group (11.28 ± 1.18, p = 0.0409). Finally, individuals from the HWI group had a significantly higher frequency of CD206+CD23+IL-10+ (7.57 ± 1.96) cells compared to individuals from the NI group (0.35 ± 0.09) (p < 0.001), suggesting that activated monocytes are a potential source of regulatory cytokines during hookworm infection.

Conclusions

Natural hookworm infection induces a high frequency of circulating monocytes that present a regulatory profile and promote the downmodulation of the proinflammatory response, which may contribute to prolonged survival of the parasite in the host.
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Metadata
Title
Regulatory monocytes in helminth infections: insights from the modulation during human hookworm infection
Authors
Lívia Silva Araújo Passos
Pedro Henrique Gazzinelli-Guimarães
Tiago Antônio de Oliveira Mendes
Ana Clara Gazzinelli Guimarães
Denise da Silveira Lemos
Natasha Delaqua Ricci
Ricardo Gonçalves
Daniella Castanheira Bartholomeu
Ricardo Toshio Fujiwara
Lilian Lacerda Bueno
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2017
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/s12879-017-2366-0

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