Mycobacterium (Mtb) antigen presentation by monocyte derived dendritic cells (DC) from PPD+ healthy subjects (N) and tuberculosis patients (TB): role of DC-SIGN.

ALEMÁN M; ROMERO M; SCHIERLOH P; YOKOBORI N; GEFFNER L; MUSELLA R; CASTAGNINO J; ABBATE E; DE LA BARRERA SS; SASIAIN MC

Rio de Janeiro, Brazil.

Congreso; 13th International Congress of Immunology. ImmunoRio 2007.; 2007

Sociedade Brasileira de Imunologia (SBI).

DC phagocytose Mtb in the airway mucosa resulting in DC maturation and presentation of mycobacterial antigens that are critical for mounting a protective immune response. DC and Mtb interaction involves different receptors as the recently identified DC-SIGN that recognizes mannose-rich molecules such as ManLAM. We have previously demonstrated that irradiated Mtb induced maturation in DC from N and TB, but the latest have higher basal CD86 expression and the differentiation process is altered. Therefore, we evaluated the differences in the capacity of DC to induce specific lymphocyte (Ly) proliferation by [3H]-tymidine up-take (cpm x 103). Mtb-matured DC drove antigen proliferation in both N and TB; however, DC from TB induced lower proliferation (N: control=3±0.6 Mtb=33±3, n=6; TB: control=1.5±0,3 Mtb=14±3,n=14, Ly:DC ratio 20:1) and higher Ly:DC ratio was necessary to achieve normal levels (N:control=2,0±0,2 Mtb=38±3; TB: control=1.2±0,1 Mtb=23±3, Ly:DC ratio 10:1). Although DCSIGN expression did not shown significant differences between N and TB (MFI: N=443±32, TB=600±152), Mtb induced the down-regulation of DC-SIGN only in N (MFI: N=240±26; TB=553±100) and, DC-SIGN blockage strictly affected proliferation in N (20±3; p<0.03) correlating with the proliferation index (N: p<0.04; r2=0.93, n=6). On the contrary, DC-SIGN blockage reduced in the same extent the proliferation induced by ManLAM in both groups and, no differences were observed in N and TB when Mtb employs other receptors to entry to DC (ie: cross-presentation). Although, the fine mechanism remains to be established, we hypothesize that the impaired antigen presentation in TB is ascribed to differences in DC-SIGN route.