Human memory-like NK cells migrating to tuberculous pleural fluid via IP-10/CXCR3 and SDF-1/CXCR4 axis produce IFN-γ in response to Bacille Calmette Guerin

- NK cells from PFCs expressed significantly higher level of CXCR3 and CXCR4.
- Memory NK cells increased CXCR3 but decreased CXCR4 than naïve NK cells form PFCs.
- NK cells in PF were more migrated in response to IP-10 and SDF-1 than PBMCs.
- CD45RO+ NK cells induced higher level of IFN-γ, which was IL-12-dependent.

We have previously shown that human memory-like NK cells were persistent in tuberculous pleurisy but it was unclear how NK cells migrated into the pleural fluids. At present, we found that NK cells from TB pleural fluid cells (PFCs) expressed significantly higher levels of CXCR3 and CXCR4 than NK cells from PBMCs. Migration assay demonstrated that IP-10 and SDF-1 induced more migration of NK cells from PFCs than PBMCs. CD45RO+ or CD45RO− NK cells from PFCs were co-cultured with autologous monocytes and stimulated with BCG. The results showed CD45RO+ but not CD45RO− NK cells produced significantly higher levels of IFN-γ, which was IL-12-dependent since anti-IL-12Rβ1 mAbs could significantly inhibit the IFN-γ by NK cells. Collectively, our data demonstrated that human Mycobacterium tuberculosis-specific NK cells were migrated into the local site of TB infection mainly via IP-10/CXCR3 and SDF-1/CXCR4 axis, memory-like NK cells might display an important role against M. tuberculosis infection.