Monocytes and neutrophils from tuberculosis patients are insensitive to anti-inflammatory effects triggered by the prototypic formyl peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP)

SUMMARY Tuberculosis is a chronic infectious disease caused by Mycobacterium tuberculosis where formyl peptides, which are cleavage products of bacterial and mitochondrial proteins, are present. In this study, we demonstrated that interferon gamma (IFN)- g and interleukin (IL)-10 induced the overexpression of the receptor for the Fc portion of IgG I (Fc g RI) in monocytes from tuberculosis (TB) patients, showing that these cells respond to IFN- g and IL-10 signals. We also demonstrated that lower doses of IL-10 render monocytes from TB patients less responsive to higher doses of the cytokine. Although the prototypic formyl peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP) is a well-known proinflammatory agonist, we have demonstrated previously that preincubation of monocytes with FMLP inhibited the up-regulation of Fc g RI induced by IFN- g or IL-10. This effect was not observed in monocytes from TB patientes. FMLP also induced the down-regulation of the expression of Fc g RI in monocytes that had been activated already with IFN- g . However, this effect of FMLP was not observed in monocytes from TB patients and supernatants from monocytes obtained from these patients were incapable of inducing the down-regulation of Fc g RI. In contrast to normal donors, supernatants from FMLP-treated neutrophils from TB patients did not modify the basal level of expression of Fc g RI in monocytes from normal donors. In conclusion, in this study we demonstrated the existence of two novel mechanisms that may contribute to the pathological effects generated by M. tuberculosis : the enhancement of Fc g RI in response to IFN- g and IL-10, and the unresponsiveness to the anti-inflammatory effects induced by formyl peptides.