AUTHOR=Ruohtula Terhi , Kondrashova Anita , Lehtonen Jussi , Oikarinen Sami , Hämäläinen Anu-Maaria , Niemelä Onni , Peet Aleksandr , Tillmann Vallo , Nieminen Janne K. , Ilonen Jorma , Knip Mikael , Vaarala Outi , Hyöty Heikki , the DIABIMMUNE Study Group , Knip Mikael , Härkönen Taina , Ryhänen Samppa , Siljander Heli , Koski Katriina , Koski Matti , Nieminen Janne , Ruohtula Terhi , Vaarala Outi , Niemelä Onni , Hämäläinen Anu-Maaria , Ormisson Anne , Peet Aleksandr , Tillmann Vallo , Ulich Valentina , Kuzmicheva Elena , Mokurov Sergei , Markova Svetlana , Pylova Svetlana , Isakova Marina , Shakurova Elena , Petrov Vladimir , Dorshakova Natalya V. , Karapetyan Tatyana , Varlamova Tatyana , Ilonen Jorma , Kiviniemi Minna , Alnek Kristi , Janson Helis , Uibo Raivo , Salum Tiit , von Mutius Erika , Weber Juliane , Ahlfors Helena , Kallionpää Henna , Laajala Essi , Lahesmaa Riitta , Lähdesmäki Harri , Moulder Robert , Hyöty Heikki , Honkanen Hanna , Kondrashova Anita , Oikarinen Sami , Harmsen Hermie J. M. , De Goffau Marcus C. , Welling Gjalt , Alahuhta Kirsi , Virtanen Suvi M. TITLE=Immunomodulatory Effects of Rhinovirus and Enterovirus Infections During the First Year of Life JOURNAL=Frontiers in Immunology VOLUME=11 YEAR=2021 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2020.567046 DOI=10.3389/fimmu.2020.567046 ISSN=1664-3224 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.