Hookworm treatment induces a decrease of suppressive regulatory T cell associated with a Th2 inflammatory response

PLoS One. 2021 Jun 10;16(6):e0252921. doi: 10.1371/journal.pone.0252921. eCollection 2021.

Abstract

Background: Like other helminths, hookworms (HW) induce a regulatory immune response able to modulate and dampen reactivity of the host to antigens. No data about the evolution of the immune response after treatment are available. We aim to phenotype the regulatory immune response during natural HW infection and its evolution after treatment.

Methodology: Twenty hookworm infected (HW+) and 14 non-infected subjects HW-from endemic area in the periphery of Ho Chi Minh City were included. Blood and feces samples were obtained before, 2 and 4 weeks after treatment with Albendazole 400mg. Additional samples were obtained at 3 and 12 months in the HW+ group. Hematological parameters, Treg (CD4+CD25hiFoxP3hi) and surface molecules (CD39, CD62L, ICOS, PD-1, CD45RA) were measured as well as inflammatory and lymphocytes differentiation cytokines such as IL-1β, IL-6, IFNγ, IL-4, IL-17, IL-10, IL-2 and TGFβ.

Results: HW+ subjects showed higher Treg, TregICOS+, Treg PD1-, TregCD62L+ and CD45RA+FoxP3lo resting Treg (rTreg). CD45RA-FoxP3lo non-suppressive Treg cells were also increased. No preferential Th1/Th2 orientation was observed, nor difference for IL-10 between two groups. After treatment, Treg, TregICOS+, TregCD62L+, Treg PD1- and rTreg decreased while IL-4 and IL-6 cytokines increased.

Conclusion: During HW infection, Treg are increased and characterized by a heterogeneous population: a highly suppressive as well as a non-suppressive T cells phenotype. After treatment, Treg with immune-suppressive phenotype exhibited a decrease parallel to an inflammatory Th2 response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Albendazole / administration & dosage*
  • Albendazole / pharmacology
  • Ancylostomatoidea / immunology*
  • Animals
  • Anthelmintics / administration & dosage*
  • Anthelmintics / pharmacology
  • Blood / parasitology
  • Case-Control Studies
  • Cytokines / metabolism
  • Feces / parasitology
  • Gene Expression Regulation / drug effects
  • Hookworm Infections / drug therapy*
  • Hookworm Infections / immunology
  • Humans
  • Middle Aged
  • T-Lymphocytes, Regulatory / immunology*
  • Th2 Cells / immunology*
  • Young Adult

Substances

  • Anthelmintics
  • Cytokines
  • Albendazole

Grants and funding

This study was supported by Académie de recherche et d'enseignement supérieur (ARES-CUD) in the form of a grant awarded to OM (PIC O MICHEL 2012-2016), the Brugmann Foundation in the form of a grant awarded to VD (Grant 2014), and Ars Statistica in the form of a salary for JFF. The specific roles of these authors are articulated in the ‘author contributions’ section. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.