Monocytes and neutrophils from tuberculosis patients are insensitive to anti-inflammatory effects triggered by a prototypic n-formyl peptide (fmlp).

BEIGIER-BOMPADRE, MACARENA; ALEMÁN, MERCEDES; BARRIONUEVO, PAULA; FRANCO, MARÍA CLARA; RUBEL, CAROLINA; PALERMO, MARINA; ABBATE, EDUARDO; SASIAIN, MARÍA DEL CARMEN; ISTURIZ, MARTÍN

La Habana, Cuba.

Congreso; VIº Congreso Latinoamericano de Inmunología.; 2002

Asociación Latinoamericana de Inmunología (ALAI)

The N-formyl peptides are products released during a chronic infection caused by Mycobacterium tuberculosis, and other bacterial infections. We evaluated the effect of the prototypic formyl peptide FMLP in the expression of the receptor for the Fc portion of IgGI (FcgRI) in monocytes from tuberculosis patients (TB). We obtained PBMC from 12 patients (HIV-) and demonstrate that IFN-g (240 U/ml) and IL-10 (100 U/ml) induce the overexpression of  FcgRI after 24h of incubation (p<0.05). The expression of FcgRI was evaluated by flow cytometry and monocytes were identified as CD14+ cells. Although FMLP is a pro-inflammatory agonist, preincubation of monocytes from normal donors (N) with FMLP (10-6M) reduce the upregulation of FcgRI induced by IFN-g or IL-10. This effect is not observed in TB monocytes (MFI ± SEM; N: IFN-g: 212±30; FMLP+IFN-g: 104±18*; p<0.05; TB: IFN-g: 141±23; FMLP+IFN-g: 127±14). In contrast to supernatants from N monocytes, supernatants from TB monocytes treated with IFN-g+FMLP do not downregulate FcgRI when added to naive N monocytes for 3h. However, supernatants from N monocytes downregulate FcgRI in TB monocytes. TB monocytes transduce signals from FMLP receptors and show an enhanced secretion of reactive oxygen species as evaluated by the reduction of Nitroblue Tetrazolium. In contrast to N neutrophils, supernatants from TB neutrophils treated with FMLP do not downregulate FcgRI when added to N monocytes for 3h. In conclusion, we show two novel mechanisms contributing to the pathological effects of M. tuberculosis: the enhancement of FcgRI in response to IFN-g and IL-10, and the unresponsiveness to the downregulatory effects of N-formyl peptides.