Blockade of C5aR1 resets M1 via gut microbiota-mediated PFKM stabilization in a TLR5-dependent manner

Increased researches show that complement, the codominant central mediator of humoral immunity, is a critical factor in tumor initiation, development, and chemotherapy resistance. C5a/C5aR1 signaling has been shown to promote tumor progression by recruiting MDSCs in breast malignancies And blockade of C5aR1 resets M1 via gut microbiota-mediated PFKM stabilization in a TLR5-dependent manner. We here report that TLR5 as a key regulator of tumor associated macrophages M1 polarization. Flagellin, the protein subunit of the bacterial flagellum, stimulates the innate immune receptor Toll-like receptor 5 (TLR5) after pattern recognition. Receptor activity was turned by a TLR5-flagellin interaction distal to the site of pattern recognition. Thus, activation of downstream signaling pathway is promoted. To investigate the role of C5aR1 in regulating TAMs M1 polarization. We cultured the primary Bone marrow-derived macrophages from wild-type and C5ar1-/- mice.