New paper by the Uguccioni Lab on the defect in migration of CCR6+ lymphocytes in HIV-1+ patients, and its correlation with a state of chronic immune activation

on December 15, 2016

The work published in the Journal of Immunology on November 28^th  by Valentina Cecchinato et al. in the group of Mariagrazia Uguccioni, is the results of a collaboration with the Divisions of infectious diseases of the Regional Hospital of Lugano and of the University of Zurich, and the German primate Center of the University of Göttingen. The work was supported by the Swiss National Foundation for Science and the European Commission.

HIV-1‑infected individuals receiving clinically effective anti-retroviral therapy (ART), rarely achieve T cell repopulation of the gut. Alterations in the integrity of the mucosal barrier have been indicated as cause for chronic immune activation and disease progression. The work presents 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.

Figure: Expression of the chemokine CCL20, which selectively recruit CCR6+ cells, in the human intestine

CCR6⁺ and CXCR3⁺ T‑helper cells accumulate in the blood of aviremic HIV-1‑infected patients on long-term ART, and their frequency in the circulation positively correlates to levels of sCD14 in plasma, a marker of chronic immune activation. T‑helper 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 hyper-activation of cofilin and inefficient actin polymerization.

Taking advantage of models of HIV infection and chronic immune activation, it has been demonstrated that the expression of the selective chemokines for the CCR6 and CXCR3 receptors, CCL20 and CXCL10, is not altered during infection, and 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.