miR-30c is specifically repressed in patients with active pulmonary tuberculosis

SPINELLI SILVANA; FERNANDEZ ROCIO DEL VALLE; ZOFF LUCIANA; BONGIOVANNI BETTINA; DIAZ ARIANA; D'ATTILIO LUCIANO; SANTUCCI NATALIA; ALVAREZ TOMAS; MARCHESINI MARCELA; BOGUÉ CRISTINA; BAY MARÍA LUISA; BOTTASSO OSCAR

Tuberculosis (Edinb)

CHURCHILL LIVINGSTONE

Año: 2017 vol. 105 p. 73 - 79

1472-9792

Tuberculous pleurisy (PLTB) is a common form of extrapulmonary tuberculosis. It often resolves withoutchemotherapy being hence considered a rather benign manifestation of the disease. Patients with PLTBmount an effective anti-mycobacterial response, unlike those with active pulmonary TB (pTB) that wereshown to present an imbalance in plasma immune and endocrine mediators. In this work, we exploredwhether expression of the active isoform of the glucocorticoid receptor (hGRa) in the context of theinflammatory-anti-inflammatory responses of TB patients may be associated to microRNA levels. Asexpected, the inflammatory response triggered in patients coexists with increased circulating cortisoland altered hGRa levels in the peripheral blood mononuclear cells. However, while hGRa expression issignificantly downregulated in PLTB, its levels in pTB patients are higher within the control values. Theseresults point out to the existence of an additional mechanism tending to preserve hGRa levels probably to deal with the chronic inflammation observed in pTB. In this regard, we found that miR-30c is strongly downregulated in mononuclear cells of pTB patients compared to PLTB cases, showing an expression profile opposite to that seen with hGRa. Interestingly, low levels of miR-30c are specific for this active form of TB, as its expression is not altered in mononuclear cells from either healthy controls or patients with tuberculous or non-tuberculous pleurisy. Moreover, miR-30c and hGRa also showed an inverse expression pattern in M. tuberculosis-stimulated THP-1 macrophage cultures. In sum, our studies identify miR-30c as a specific correlate of pulmonary manifestations of TB, potentially involved in the altered glucocorticoid sensitivity observed in these patients.