Functionally relevant decreases in activatory receptor expression on NK cells are associated with pulmonary tuberculosis in vivo and persist after successful treatment

Federica Bozzano, Paola Costa, Giovanni Passalacqua, Ferdinando Dodi, Silvia Ravera, Gabriella Pagano, Giorgio W. Canonica, Lorenzo Moretta, Andrea De Maria

Research output: Contribution to journalArticle

Abstract

Correlates for the initiation of Mycobacterium tuberculosis hominis (Mth) replication from latency are needed in order to improve Mth control. In order to analyze if perturbations of peripheral NK cells may be associated with exit from Mth latency, sequential patients with newly diagnosed lung tuberculosis (TB) were studied. Peripheral NK cells were analyzed by cytofluorometry, in vitro culture and functional assays. At the onset of lung TB, imbalances in NK cell subsets were evident. Decreased CD56brightCD16+/- subsets with significantly compromised NKp30 and NKp46 expression and with specifically decreased γ-IFN production upon triggering were evident. These features were not completely restored when purified NK cells were cultured in vitro. Culture supplementation with α-IFN increased only NKp30 expression in TB and healthy donors. Extensive peripheral NK cell triggering was evident in these patients, as shown by the expression of NK cell activation markers and of the lymph node-homing chemokine receptor CCR7 on CD16+ CD56dull cells. Significant persistence of decreased NKp30 and NKp46 after successful treatment with a standard four-drug regimen was detected after full recovery. NK cell function is deeply affected in patients at the onset of pulmonary TB. The involvement of multiple activatory receptors may provide a relevant contribution to the spread of mycobacteria exiting from latency.

Original languageEnglish
Pages (from-to)779-791
Number of pages13
JournalInternational Immunology
Volume21
Issue number7
DOIs
Publication statusPublished - 2009

Keywords

  • α-IFN
  • Immunoreconstitution
  • Latency
  • Mth
  • NK cells
  • Pulmonary tuberculosis

ASJC Scopus subject areas

  • Immunology

Fingerprint Dive into the research topics of 'Functionally relevant decreases in activatory receptor expression on NK cells are associated with pulmonary tuberculosis in vivo and persist after successful treatment'. Together they form a unique fingerprint.

  • Cite this