Roles of SOCS1 for establishment of mycobacterial infection

Abstract

Abstract Background Suppressor of cytokine signaling (SOCS) 1 plays a crucial role in the negative regulation of JAK/STAT pathway. The SOCS1 is strongly upregulated by infection with several pathogens include M. bovis bacillus Calmette-Guérin (BCG). Since the function of SOCS1 induced by infection is not fully understood. In present study, we establish recombinant BCG which express a dominant-negative SOCS1 (rBCG-SOCS1DN) which acts as antagonist for SOCS1 signals. Methods C57BL/6, Rag1−/−, Nos2−/− and Rag1−/−Nos2−/− (DKO) mice were inoculated intratracheally with rBCGSOCS1DN or vector control rBCG (rBCG-pSO). Lungs and bronchoalveolar lavage fluids were harvested and analyzed. The mRNA and supernatants from bone marrow-derived myeloid dendritic cells (BMmDCs) infected with rBCG were harvested and nos2 gene expression and the production of nitric oxcide (NO) were measured. These cells were analized by electron microscopy. Results The amount of rBCG-SOCS1DN was significantly reduced by not only C57BL/6 but also Rag1−/− mice comparison with those of rBCG-pSO. The cytokine/chemokine profiles were not significant difference between rBCG-SOCS1DN and rBCG-pSO; however, nos2 gene expression and NO release from BMmDCs infected with rBCG-SOCS1DN were significantly higher than BMmDCs infected with rBCG-pSO. In Nos2−/− and DKO mice, there were no significant difference of bacterial burdens between rBCG-SOCS1DN and rBCG-pSO. Furthermore, the BMmDCs infected rBCG-SOCS1DN were necrotic damaged less than BMmDCs infected with rBCG-pSO. Conclusions These data suggest that BCG induce SOCS1 activation for evasion of microbicidal mechanism by nitric oxide from the innate immune responses.