Frontiers in Immunology (Feb 2021)
Immunomodulatory Effects of Rhinovirus and Enterovirus Infections During the First Year of Life
- Terhi Ruohtula,
- Anita Kondrashova,
- Jussi Lehtonen,
- Sami Oikarinen,
- Anu-Maaria Hämäläinen,
- Onni Niemelä,
- Aleksandr Peet,
- Vallo Tillmann,
- Janne K. Nieminen,
- Jorma Ilonen,
- Mikael Knip,
- Mikael Knip,
- Mikael Knip,
- Mikael Knip,
- Outi Vaarala,
- Heikki Hyöty,
- Heikki Hyöty,
- the DIABIMMUNE Study Group,
- Mikael Knip,
- Taina Härkönen,
- Samppa Ryhänen,
- Heli Siljander,
- Katriina Koski,
- Matti Koski,
- Janne Nieminen,
- Terhi Ruohtula,
- Outi Vaarala,
- Onni Niemelä,
- Anu-Maaria Hämäläinen,
- Anne Ormisson,
- Aleksandr Peet,
- Vallo Tillmann,
- Valentina Ulich,
- Elena Kuzmicheva,
- Sergei Mokurov,
- Svetlana Markova,
- Svetlana Pylova,
- Marina Isakova,
- Elena Shakurova,
- Vladimir Petrov,
- Natalya V. Dorshakova,
- Tatyana Karapetyan,
- Tatyana Varlamova,
- Jorma Ilonen,
- Minna Kiviniemi,
- Kristi Alnek,
- Helis Janson,
- Raivo Uibo,
- Tiit Salum,
- Erika von Mutius,
- Juliane Weber,
- Helena Ahlfors,
- Henna Kallionpää,
- Essi Laajala,
- Riitta Lahesmaa,
- Harri Lähdesmäki,
- Robert Moulder,
- Heikki Hyöty,
- Hanna Honkanen,
- Anita Kondrashova,
- Sami Oikarinen,
- Hermie J. M. Harmsen,
- Marcus C. De Goffau,
- Gjalt Welling,
- Kirsi Alahuhta,
- Suvi M. Virtanen
Affiliations
- Terhi Ruohtula
- Clinicum, University of Helsinki, Helsinki, Finland
- Anita Kondrashova
- Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
- Jussi Lehtonen
- Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
- Sami Oikarinen
- Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
- Anu-Maaria Hämäläinen
- Department of Pediatrics, Jorvi Hospital, Helsinki University Hospital, Espoo, Finland
- Onni Niemelä
- Department of Laboratory Medicine and Medical Research Unit, Seinäjoki Central Hospital and University of Tampere, Seinäjoki, Finland
- Aleksandr Peet
- Department of Pediatrics, University of Tartu and Tartu University Hospital, Tartu, Estonia
- Vallo Tillmann
- Department of Pediatrics, University of Tartu and Tartu University Hospital, Tartu, Estonia
- Janne K. Nieminen
- Pediatric Research Center, Children’s Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
- Jorma Ilonen
- Immunogenetics Laboratory, University of Turku, Turku, Finland
- Mikael Knip
- Pediatric Research Center, Children’s Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
- Mikael Knip
- Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland
- Mikael Knip
- Folkhälsan Research Center, Helsinki, Finland
- Mikael Knip
- 0Tampere Center for Child Health Research, Tampere University Hospital, Tampere, Finland
- Outi Vaarala
- Clinicum, University of Helsinki, Helsinki, Finland
- Heikki Hyöty
- Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
- Heikki Hyöty
- 1Fimlab Laboratories, Pirkanmaa Hospital District, Tampere, Finland
- the DIABIMMUNE Study Group
- Mikael Knip
- Taina Härkönen
- Samppa Ryhänen
- Heli Siljander
- Katriina Koski
- Matti Koski
- Janne Nieminen
- Terhi Ruohtula
- Outi Vaarala
- Onni Niemelä
- Anu-Maaria Hämäläinen
- Anne Ormisson
- Aleksandr Peet
- Vallo Tillmann
- Valentina Ulich
- Elena Kuzmicheva
- Sergei Mokurov
- Svetlana Markova
- Svetlana Pylova
- Marina Isakova
- Elena Shakurova
- Vladimir Petrov
- Natalya V. Dorshakova
- Tatyana Karapetyan
- Tatyana Varlamova
- Jorma Ilonen
- Minna Kiviniemi
- Kristi Alnek
- Helis Janson
- Raivo Uibo
- Tiit Salum
- Erika von Mutius
- Juliane Weber
- Helena Ahlfors
- Henna Kallionpää
- Essi Laajala
- Riitta Lahesmaa
- Harri Lähdesmäki
- Robert Moulder
- Heikki Hyöty
- Hanna Honkanen
- Anita Kondrashova
- Sami Oikarinen
- Hermie J. M. Harmsen
- Marcus C. De Goffau
- Gjalt Welling
- Kirsi Alahuhta
- Suvi M. Virtanen
- DOI
- https://doi.org/10.3389/fimmu.2020.567046
- Journal volume & issue
-
Vol. 11
Abstract
Early childhood infections have been implicated in the development of immune-mediated diseases, such as allergies, asthma, and type 1 diabetes. We set out to investigate the immunomodulatory effects of early viral infections experienced before the age of one year on the peripheral regulatory T cell population (Treg) and circulating cytokines in a birth-cohort study of Estonian and Finnish infants. We show here a temporal association of virus infection with the expression of FOXP3 in regulatory T cells. Infants with rhinovirus infection during the preceding 30 days had a higher FOXP3 expression in Treg cells and decreased levels of several cytokines related to Th1 and Th2 responses in comparison to the children without infections. In contrast, FOXP3 expression was significantly decreased in highly activated (CD4+CD127−/loCD25+FOXP3high) regulatory T cells (TregFOXP3high) in the infants who had enterovirus infection during the preceding 30 or 60 days. After enterovirus infections, the cytokine profile showed an upregulation of Th1- and Th17-related cytokines and a decreased activation of CCL22, which is a chemokine derived from dendritic cells and associated with Th2 deviation. Our results reveal that immunoregulatory mechanisms are up-regulated after rhinovirus infections, while enterovirus infections are associated with activation of proinflammatory pathways and decreased immune regulation.
Keywords
