Our study revealed an unprecedented efficient ‘fishing nets’ hunting paradigm of macrophages to fight against severe bacterial infection: (1) upon encountering Gram-negative bacteria, macrophages initiate the formation of dendrite-like pseudopods (DLPs) with blunt, bean sprout-like tips; (2) the function of DLPs is to enhance the internalization of bacteria digestion; (3) the underlying molecular mechanism of DLPs formation involves the LPS-TLR4-NF-κB-ARHGEF3-RhoA-cytoskeletal assembly. This evidence concerns the gene ARHGEF3 and bacterial infectious disease.