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Selectin Ligand-Independent Priming and Maintenance of T Cell Immunity during Airborne Tuberculosis¹

Tanja Schreiber^2,*,, Stefan Ehlers^2,, Sahar Aly, Alexandra Hölscher^*,, Sven Hartmann, Martin Lipp, John B. Lowe and Christoph Hölscher^3,*

^* Junior Research Group Molecular Infection Biology, Research Center Borstel, and Division of Molecular Infection Biology, Research Center Borstel, Borstel, Germany; Department of Tumor Genetics and Immunogenetics, Max-Delbrück-Center for Molecular Medicine, Berlin, Germany; and Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH 44106

Immunity to Mycobacterium tuberculosis infection is critically dependent on the timely priming of T effector lymphocytes and their efficient recruitment to the site of mycobacterial implantation in the lung. E-, P-, and L-selectin counterreceptors control lymphocyte homing to lymph nodes and leukocyte trafficking to peripheral sites of acute inflammation, their adhesive function depending on fucosylation by fucosyltransferases (FucT) IV and VII. To address the relative importance of differentially glycosylated selectin counterreceptors for priming of T cell effector functions in a model of mycobacteria-induced granulomatous pulmonary inflammation, we used aerosol-borne M. tuberculosis to infect FucT-IV^–/–, FucT-VII^–/–, FucT-IV^–/–/FucT-VII^–/–, or wild-type control mice. In lymph nodes, infected FucT-IV^–/–/FucT-VII^–/– and, to a lesser extent, FucT-VII^–/– mice had severely reduced numbers of T cells and reduced Ag-specific effector responses. By contrast, recruitment of activated T cells into the lungs was similar in all four groups of mice during infection and expression of T cell, and macrophage effector functions were only delayed in lungs of FucT-IV^–/–/FucT-VII^–/– mice. Importantly, lungs from all groups expressed CXCL13, CCL21, and CCL19 and displayed organized follicular neolymphoid structures after infection with M. tuberculosis, which suggests that the lung served as a selectin ligand-independent priming site for immune responses to mycobacterial infection. All FucT-deficient strains were fully capable of restricting M. tuberculosis growth in infected organs until at least 150 days postinfection. Our observations indicate that leukocyte recruitment functions dictated by FucT-IV and FucT-VII-dependent selectin ligand activities are not critical for inducing or maintaining T cell effector responses at levels necessary to control pulmonary tuberculosis.

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