Spontaneous or Mycobacterium tuberculosis-induced apoptotic neutrophils exert opposite effects on dendritic cell-mediated immune response.

ALEMÁN M, DE LA BARRERA S, SCHIERLOH P, YOKOBORI N, BALDINI M, MUSELLA R, ABBATE E, SASIAIN M.

EUROPEAN JOURNAL OF IMMUNOLOGY

WILEY-VCH

Lugar: weinheim; Año: 2007 vol. 37 p. 1524 - 1537

0014-2980

PMN modulate adaptive immune response through interactions with iDCs while apoptotic PMN (PMNapo) may have an inhibitory effect on DC functions. We investigate the effect exerted by PMNapo in DCs maturation and the role of Mycobacterium tuberculosis (Mtb)-induced apoptotic PMN in the cross-presentation of mycobacterial antigens. We demonstrate that Mtb triggers the maturation of iDC while it is impaired by the presence of PMNapo, which abrogate Mtb-induced expression of costimulatory and HLA class II molecules, reducing IL-12 and IFN-g release by DCs and partially inhibiting Mtb-driven lymphocyte proliferation. This inhibitory effect is not observed in already Mtb-matured DCs, and involves a direct interaction between DCs and PMNapo since supernatants from PMNapo cultures have no effect. Although PMNapo do not alter Mtb/DC-SIGN interaction they affect the intracellular signals leading to DCs maturation without requiring their entry into DCs. Phagocytosis of Mtb-induced apoptotic PMN by iDC leads to lymphoproliferation which is significantly reduced by blocking CD36 and not DC-SIGN on iDC. Therefore, cross-presentation of Mtb antigens is taking place. Our findings suggest that the inflammatory milieu is subjected to a fine balance between non-infected and Mtb-induced apoptotic PMN: non-infected PMNapo limiting inflammation and Mtb-induced apoptotic PMN generating a specific immune activity.