Modified Vaccinia virus Ankara but not vaccinia virus induces chemokine expression in cells of the monocyte/macrophage lineage.

BACKGROUND

The orthopoxvirus strain Modified Vaccinia virus Ankara (MVA) rapidly induces innate immune responses. Previously, we demonstrated that CCL2 and CCR1 are important players in MVA induced recruitment of leukocytes to the lung. Alveolar macrophages are sentinel cells in the lung, which are likely amongst the first cells of the immune system to encounter and respond to virus during respiratory infection. Therefore we examined the potential of the murine alveolar macrophage MH-S cell line as a model to study chemokine expression during infection with MVA and vaccinia virus (VACV) strain Western Reserve (WR).

FINDINGS

MVA but not VACV infected MH-S cells increased the expression of the CXCR2 acting chemokine CXCL2. MH-S cells constitutively produced CCL2 and CCR1 acting chemokines CCL3, CCL5 and CCL9. Consequently, supernatants of mock treated and virus infected MH-S cells induced chemotaxis of murine promyelocyte MPRO cells and human monocytic THP-1 cells at the same level. However, supernatants of MVA infected MH-S cells significantly increased chemotaxis of the CCR2 deficient human monocytic cell line U-937. Chemotaxis of all three cell types was inhibited by J 113863, a CCR1 antagonist. Additionally, we show that MVA but not VACV WR infection of THP-1 cells induces expression of C-C motif and C-X-C motif chemokines and generates a chemotactic activity for monocytes, which was J 113863 sensitive.

CONCLUSIONS

These results extend our previous findings, demonstrating that MVA but not VACV WR induces chemokine production in alveolar macrophages and monocytes, which can induce recruitment of monocytes in a CCR1 dependent manner.