MicroRNA miR-223 constrains lethal inflammation during Mycobacterium tuberculosis infection

The molecular mechanisms that control innate cell recruitment during chronic infection and inflammation, such as tuberculosis (TB), are incompletely understood. During TB, myeloid cells infiltrate the lung and sustain local inflammation. We identified microRNA (miR)-223 as one of the most abundant noncoding RNAs in lung parenchyma of TB patients and susceptible mice. MiR-223 controlled lung recruitment of myeloid cells, and consequently, neutrophil-driven lethal inflammation, by directly targeting the chemoattractants CXCL2, CCL3 and IL-6. Our study reveals an essential role for a single miR in TB. Moreover, we identify new targets for and assign novel biological functions to miR-223. By regulating leukocyte chemotaxis via chemoattractants, miR223 is critical for control of TB and probably other nonresolving inflammatory diseases. MicroRNAs expression analysis in whole blood from 8 TB and 8 TST+ subjects. The samples were collected at Makerere University in Kampala, Uganda. Gene expression analysis of whole blood and lung tissue of C57/BL6 and miR-223-/- mouse strains (8-12 weeks of age) after Mtb aerosol infection. Samples were collected at 7, 14 and 21 days post infection.