Università della Svizzera italiana

Memory T cells in latent mycobacterium tuberculosis infection are directed against three antigenic islands and largely contained in a CXCR3+CCR6+ Th1 subset

Lindestam Arlehamn, Cecilia S. ; Gerasimova, Anna ; Mele, Federico ; Henderson, Ryan ; Swann, Justine ; Greenbaum, Jason A. ; Kim, Yohan ; Sidney, John ; James, Eddie A. ; Taplitz, Randy ; McKinney, Denise M. ; Kwok, William W. ; Grey, Howard ; Sallusto, Federica ; Peters, Bjoern ; Sette, Alessandro

In: Plos pathogens, 2013, vol. 9, no. 1, p. e1003130

An understanding of the immunological footprint of Mycobacterium tuberculosis (MTB) CD4 T cell recognition is still incomplete. Here we report that human Th1 cells specific for MTB are largely contained in a CXCR3+CCR6+ memory subset and highly focused on three broadly immunodominant antigenic islands, all related to bacterial secretion systems. Our results refute the notion that secreted...

Università della Svizzera italiana

Immunological consequences of intragenus conservation of Mycobacterium tuberculosis T-cell epitopes

Lindestam Arlehamn, Cecilia S. ; Paul, Sinu ; Mele, Federico ; Huang, Charlie ; Greenbaum, Jason A. ; Vita, Randi ; Sidney, John ; Peters, Bjoern ; Sallusto, Federica ; Sette, Alessandro

In: Proceedings of the national academy of sciences of the United States of America, 2015, vol. 112, no. 2, p. E147-E155

A previous unbiased genome-wide analysis of CD4 Mycobacterium tuberculosis (MTB) recognition using peripheral blood mononuclear cells from individuals with latent MTB infection (LTBI) or nonexposed healthy controls (HCs) revealed that certain MTB sequences were unexpectedly recognized by HCs. In the present study, it was found that, based on their pattern of reactivity, epitopes could be...

Università della Svizzera italiana

Human IFN-γ immunity to mycobacteria is governed by both IL-12 and IL-23

Markle, Janet G. ; Martínez-Barricarte, Rubén ; Ma, Cindy S. ; Deenick, Elissa K. ; Ramírez-Alejo, Noé ; Mele, Federico ; Latorre, Daniela ; Mahdaviani, Seyed Alireza ; Aytekin, Caner ; Mansouri, Davood ; Bryant, Vanessa L. ; Jabot-Hanin, Fabienne ; Deswarte, Caroline ; Nieto-Patlán, Alejandro ; Surace, Laura ; Kerner, Gaspard ; Itan, Yuval ; Jovic, Sandra ; Avery, Danielle T. ; Wong, Natalie ; Rao, Geetha ; Patin, Etienne ; Okada, Satoshi ; Bigio, Benedetta ; Boisson, Bertrand ; Rapaport, Franck ; Seeleuthner, Yoann ; Schmidt, Monika ; Ikinciogullari, Aydan ; Dogu, Figen ; Tanir, Gonul ; Tabarsi, Payam ; Bloursaz, Mohammed Reza ; Joseph, Julia K. ; Heer, Avneet ; Kong, Xiao-Fei ; Migaud, Mélanie ; Lazarov, Tomi ; Geissmann, Frédéric ; Fleckenstein, Bernhard ; Lindestam Arlehamn, Cecilia ; Sette, Alessandro ; Puel, Anne ; Emile, Jean-François ; Vosse, Esther van de ; Quintana-Murci, Lluis ; Di Santo, James P. ; Abel, Laurent ; Boisson-Dupuis, Stéphanie ; Bustamante, Jacinta ; Tangye, Stuart G. ; Sallusto, Federica ; Casanova, Jean-Laurent

In: Science Immunology, 2018, vol. 3, no. 30, p. eaau6759

Hundreds of patients with autosomal recessive, complete IL-12p40 or IL-12Rß1 deficiency have been diagnosed over the last 20 years. They typically suffer from invasive mycobacteriosis and, occasionally, from mucocutaneous candidiasis. Susceptibility to these infections is thought to be due to impairments of IL- 12–dependent IFN-? immunity and IL-23–dependent IL-17A/IL-17F immunity,...