Natural killer cells regulate pulmonary macrophages polarization in host defense chlamydial lung infection

NK cells and pulmonary macrophages both are important components of innate immunity. The interaction between NK cells and pulmonary macrophages during Chlamydia muridarum（C. muridarum）respiratory infections is poorly understood. In this study, we explored the effect of NK cells on regulation of pulmonary macrophage function during chlamydial lung infection. We found that NK depletion led to polarization of pulmonary macrophages from M1 to M2 phenotype, and this related to significantly reduced miR-155 expression in pulmonary macrophage. Using adoptive transfer approach, we found that the recipient mice receiving lung macrophages isolated from C. muridarum-infected NK-cell-depleted mice exhibited an increased bacterial load and severe inflammation in the lung upon chlamydial challenge when compared with the recipients of lung macrophages from infected IgG -treated mice. Herein, the effects of NK cells on macrophage polarization were examined in vitro. We found that NK cells from chlamydial-infected mice (iNK) significantly induced M1 polarization compared to that from sham-infected mice (uNK). Inhibition of miR-155 expression in macrophages attenuated M1 polarization induced by iNK, while miR-155 over-expression enhanced it. Furthermore, neutralization of IFN-γ in the coculture system decreased the expression of miR-155 by macrophages, and resulted in diminished M1 polarization induced by iNK cells. The data indicates that NK cells direct M1 polarization through up-regulation of miR-155 by IFN-γ production, and NK-regulated macrophage polarization is functionally relevant to host defense against chlamydial infection. Male BALB/c mice were maintained in a specific pathogen-free animal care facility of Shandong University. All mice used in this study were males between 6 and 8 weeks old. The experiment was divided into NK+macrophage and NK-macrophage group, N=3 per group.