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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
immunology and microbiology
Impairment of CCR6+ and CXCR3+ Th cell migration in HIV-1 infection is rescued by modulating actin polymerization
Journal of Immunology, Volume 198, No. 1, Year 2017
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Description
CD4+ T cell repopulation of the gut is rarely achieved in HIV-1-infected individuals who are receiving clinically effective antiretroviral therapy. Alterations in the integrity of the mucosal barrier have been indicated as a cause for chronic immune activation and disease progression. In this study, we present evidence that persistent immune activation causes impairment of lymphocytes to respond to chemotactic stimuli, thus preventing their trafficking from the blood stream to peripheral organs. CCR6+ and CXCR3+ Th cells accumulate in the blood of aviremic HIV-1-infected patients on long-term antiretroviral therapy, and their frequency in the circulation positively correlates to levels of soluble CD14 in plasma, a marker of chronic immune activation. Th cells show an impaired response to chemotactic stimuli both in humans and in the pathogenic model of SIV infection, and this defect is due to hyperactivation of cofilin and inefficient actin polymerization. Taking advantage of a murine model of chronic immune activation, we demonstrate that cytoskeleton remodeling, induced by okadaic acid, restores lymphocyte migration in response to chemokines, both in vitro and in vivo. This study calls for novel pharmacological approaches in those pathological conditions characterized by persistent immune activation and loss of trafficking of T cell subsets to niches that sustain their maturation and activities. Copyright © 2016 by The American Association of Immunologists, Inc.
Authors & Co-Authors
Cecchinato, Valentina
Switzerland, Lugano
Università Della Svizzera Italiana
Bernasconi, Enos
Unknown Affiliation
Speck, Roberto F.
Switzerland, Zurich
Universität Zürich
Proietti, Michele
Switzerland, Lugano
Università Della Svizzera Italiana
Sauermann, Ulrike
Germany, Gottingen
Deutsches Primatenzentrum
Schöni-Affolter, Franziska
Switzerland, Lausanne
Centre Hospitalier Universitaire Vaudois
Stahl-Hennig, Christiane P.
Germany, Gottingen
Deutsches Primatenzentrum
Aubert, Vincent
Unknown Affiliation
Battegay, Manuel
Unknown Affiliation
Böni, Jürg
Unknown Affiliation
Braun, Dominique Laurent
Unknown Affiliation
Bucher, Heíner C.C.
Unknown Affiliation
Calmy, Alexandra L.
Unknown Affiliation
Cavassini, Matthias
Unknown Affiliation
Ciuffi, Angela
Unknown Affiliation
Dollenmaier, Guenter
Unknown Affiliation
Egger, Matthias
Unknown Affiliation
Elzi, Luigia
Unknown Affiliation
Fehr, Jan Sven
Unknown Affiliation
Fellay, Jacques
Unknown Affiliation
Furrer, Hansjakob
Unknown Affiliation
Fux, Christoph Andreas
Unknown Affiliation
Günthard, Hüldrych Fritz
Unknown Affiliation
Haerry, David Hans Ulrich
Unknown Affiliation
Hasse, Barbara Katharina
Unknown Affiliation
Hirsch, Hans H.
Unknown Affiliation
Hoffmann, Matthias
Unknown Affiliation
Hösli, Irene Mathilde
Unknown Affiliation
Kahlert, Christian R.
Unknown Affiliation
Kaiser, Laurent K.
Unknown Affiliation
Keiser, Olivia
Unknown Affiliation
Klimkait, Thomas
Unknown Affiliation
Kouyos, Roger D.
Unknown Affiliation
Kovari, Helen
Unknown Affiliation
Ledergerber, Bruno
Unknown Affiliation
Martinetti, Gladys
Unknown Affiliation
Martínez de Tejada, Begoῆa
Unknown Affiliation
Marzolini, Catia
Unknown Affiliation
Metzner, Karin Jutta
Unknown Affiliation
Müller, Nicolas J.
Unknown Affiliation
Pantaleo, Giuseppe P.
Unknown Affiliation
Paioni, Paolo
Unknown Affiliation
Rauch, Andri
Unknown Affiliation
Rudin, Christoph
Unknown Affiliation
Scherrer, Alexandra U.
Unknown Affiliation
Schmid, Patrick
Unknown Affiliation
Stöckle, Marcel
Unknown Affiliation
Tarr, Philip E.
Unknown Affiliation
Trkola, Alexandra
Unknown Affiliation
Vernazza, Pietro Luigi
Unknown Affiliation
Wandeler, Gilles
Unknown Affiliation
Statistics
Citations: 19
Authors: 51
Affiliations: 6
Identifiers
Doi:
10.4049/jimmunol.1600568
ISSN:
00221767
Research Areas
Infectious Diseases