Th2/1 Hybrid Cells Occurring in Murine and Human Strongyloidiasis Share Effector Functions of Th1 Cells

Frontiers in Cellular and Infection Microbiology

Lö¹  hning, Max²  Bock, Cristin N.³  Rausch, Sebastian⁴  Rajamanickam, Anuradha⁵  Merle, Roswitha⁶  Kü⁷  Brunn, Marie-Luise⁷  Breloer, Minka⁷  hl, Anja A.⁹  Boothra, Yukhti⁹  Babu, Subash^1,10  Hartmann, Susanne^1,10 

[1] -University Medicine Berlin, Berlin, Germany;Department of Veterinary Medicine, Institute for Veterinary Epidemiology and Biostatistics, Freie UniversitäDepartment of Veterinary Medicine, Institute of Immunology, Freie UniversitäExperimental Immunology, Department of Rheumatology and Clinical Immunology, CharitéLaboratory of Parasitic Diseases, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States;Medical Department, Division of Gastroenterology, Infectiology and Rheumatology/Research Center ImmunoSciences, CharitéNational Institutes of Health-NIRT-International Center for Excellence in Research, Chennai, India;Pitzer Laboratory of Osteoarthritis Research, German Rheumatism Research Center (DRFZ), Leibniz Institute, Berlin, Germany;Section for Molecular Biology and Immunology, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany;t Berlin, Berlin, Germany

关键词: nematode;    Strongyloides;    th2;    Th2/1;    Hybrid;    T-bet;    GATA-3;    co-expression;    IFN-gamma;   

DOI  :  10.3389/fcimb.2017.00261

学科分类：生物科学（综合）

来源: Frontiers

【 摘 要 】

Infections by the soil-transmitted threadworm Strongyloides stercoralis affect 50-100 million people worldwide, predominantly in tropic and sub-tropic regions. Here we assessed the T helper cell phenotypes in threadworm-infected patients and experimental murine infections with focus on CD4+ T cells co-expressing markers of Th2 and Th1 differentiation. We show that mice infected with the close relative S. ratti generate strong Th2 responses characterized by the expansion of CD4+ GATA-3+ cells expressing IL-4/-5/-13 in blood, spleen, gut-draining lymph nodes, lung and gut tissue. In addition to conventional Th2 cells, significantly increased frequencies of GATA-3+T-bet+ Th2/1-hybrid cells were detected in all organs and co-expressed Th2- and Th1-cytokines at intermediate levels. Assessing the phenotype of blood-derived CD4+ T cells from South Indian patients infected with S. stercoralis and local uninfected control donors we found that GATA-3 expressing Th2 cells were significantly increased in the patient cohort, coinciding with elevated eosinophil and IgE/IgG4 levels. A fraction of IL-4+CD4+ T cells simultaneously expressed IFN- hence displaying a Th2/1 hybrid phenotype. In accordance with murine Th2/1 cells, human Th2/1 cells expressed intermediate levels of Th2 cytokines. Contrasting their murine counterparts, human Th2/1 hybrids were marked by high levels of IFN- and rather low GATA-3 expression. Assessing the effector function of murine Th2/1 cells in vitro we found that Th2/1 cells were qualified for driving the classical activation of macrophages. Furthermore, Th2/1 cells shared innate, cytokine-driven effector functions with Th1 cells. Hence, the key findings of our study are that T helper cells with combined characteristics of Th2 and Th1 cells are integral to immune responses of helminth-infected mice, but also occur in helminth-infected humans and we suggest that Th2/1 cells are poised for the instruction of balanced immune responses during nematode infections.

【 授权许可】

CC BY