Fachbereich Veterinärmedizin



    Th2/1 Hybrid Cells Occurring in Murine and Human Strongyloidiasis Share Effector Functions of Th1 Cells (2017)

    Zeitschriftenartikel / wissenschaftlicher Beitrag
    Bock, Cristin (WE 6)
    Babu, Subash
    Breloer, Minka
    Rajamanickam, Anuradha
    Boothra, Yukhti
    Brunn, Marie-Luise
    Kühl, Anja A.
    Merle, Roswitha
    Löhning, Max
    Hartmann, Susanne (WE 6)
    Rausch, Sebstian (WE 6)
    Frontiers in cellular and infection microbiology; Vol. 7(Article 261) — S. 1–15
    ISSN: 2235-2988
    URL (Volltext): http://journal.frontiersin.org/article/10.3389/fcimb.2017.00261/full#h1
    DOI: 10.3389/fcimb.2017.00261
    Institut für Immunologie

    Robert-von-Ostertag-Str. 7-13
    Gebäude 35
    14163 Berlin
    +49 30 838 51834

    Abstract / Zusammenfassung

    Infections by the soil-transmitted threadworm Strongyloides stercoralis affect 30–100 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-γ 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-γ 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.