miR-30cis specifically repressed in patients with active pulmonary tuberculosis

SPINELLI, SILVANA V.; BONGIOVANNI, BETTINA; SANTUCCI, NATALIA; BOGUE, CRISTINA; SPINELLI, SILVANA V.; BONGIOVANNI, BETTINA; ZOFF, LUCIANA; SANTUCCI, NATALIA; D'ATTILIO, LUCIANO; BOGUE, CRISTINA; MARCHESINI, MARCELA M.; BOTTASSO, OSCAR A.; ZOFF, LUCIANA; D'ATTILIO, LUCIANO; MARCHESINI, MARCELA M.; BOTTASSO, OSCAR A.; FERNÁNDEZ, ROCÍO DEL V.; DÍAZ, ARIANA; ALVAREZ, TOMÁS; BAY, MARIA L.; FERNÁNDEZ, ROCÍO DEL V.; DÍAZ, ARIANA; ALVAREZ, TOMÁS; BAY, MARIA L.

Tuberculosis (Edinb)

CHURCHILL LIVINGSTONE

Lugar: ESCOCIA; Año: 2017 vol. 105 p. 73 - 79

1472-9792

Tuberculous pleurisy (PLTB) is a common form of extrapulmonary tuberculosis. It often resolves without chemotherapy being hence considered a rather benign manifestation of the disease. Patients with PLTB mount an effective anti-mycobacterial response, unlike those with active pulmonary TB (pTB) that were shown to present an imbalance in plasma immune and endocrine mediators. In this work, we explored whether expression of the active isoform of the glucocorticoid receptor (hGRα) in the context of the inflammatory-anti-inflammatory responses of TB patients may be associated to microRNA levels. As expected, the inflammatory response triggered in patients coexists with increased circulating cortisol and altered hGRα levels in the peripheral blood mononuclear cells. However, while hGRα expression is significantly downregulated in PLTB, its levels in pTB patients are higher within the control values. These results point out to the existence of an additional mechanism tending to preserve hGRα 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 hGRα. Interestingly, low levels of miR-30c are specific for this active form of TB, as its expression is not altered in mononuclear cellsfrom either healthy controls or patients with tuberculous or non-tuberculous pleurisy. Moreover, miR-30c and hGRα 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