Comparative interleukins and chemokines analysis of mice mesenchymal stromal cells infected with Mycobacterium tuberculosis H37Rv and H37Ra

Abstract

Inflammatory pathways involving Mesenchymal stromal cells (MSCs) play an important role in Mycobacterium tuberculosis (Mtb) infection. H37Rv (Rv) is a standard virulent strain, however, H37Ra (Ra) is a strain with reduced virulence. Interleukins and chemokines production are known to promote inflammation resistance in mammalian cells and is recently reported to regulate mycobacterial immunopathogenesis via inflammatory responses. MSCs are very important cells during Mtb infection. However, the different expressions of interleukins and chemokines in the process of Mtb-infected MSCs between Ra and Rv remain unclear. We used the techniques of RNA-Seq, qRT-PCR, ELISA, and Western Blotting. We have shown that Rv infection significantly increased mRNA expressions of Mndal, Gdap10, Bmp2, and Lif, thereby increasing more differentiation of MSCs compared with Ra infection in MSCs. Further investigation into the possible mechanisms, we found that Rv infection enhanced more inflammatory response (Mmp10, Mmp3, and Ptgs2) through more activation of the TLR2-MAP3K1-JNK pathway than did Ra infection in MSCs. Further action showed that Rv infection enhanced more Il1α, Il6, Il33, Cxcl2, Ccl3, and Ackr3 production than did Ra infection. Rv infection showed more expressions of Mmp10, Mmp3, Ptgs2, Il1α, Il6, Il33, Cxcl2, Ccl3, and Ackr3 possibly through more active TLR2-MAP3K1-JNK pathway than did Ra infection in MSCs. MSCs may therefore be a new candidate for the prevention and treatment of tuberculosis.