Figure 2

Figure 2

The paralogs cxcr3.2 and cxcr3.3 have antagonistic functions that regulate macrophage recruitment to sites of infection. Cxcr3.2 (orange) is a functional homolog of human Cxcr3 required for macrophage recruitment to sites of infection and other inflammatory settings. Cxcr3.3 (dark red) displays the structural of Ackrs such as the substitution of the central Arginine (R) of the highly conserved E/DRY-motif for a Cysteine (DCY) that prevents canonical GPCR signaling (arrow). Cxcr3.3 regulates Cxcr3.2-mediated macrophage recruitment through its scavenging function (blunt arrow) of Cxcl11-like chemokines (blue dots). (A) Shows how macrophages infected with M. marinum (purple rods) recruit non-infected macrophages through the secretion of Cxcl11-like chemokines to contain the bacterial infection and to clear dying macrophages in wt zebrafish larvae. (B) shows how macrophage recruitment is reduced in cxcr3.2 mutants (as an actively signaling chemokine is depleted) and how fewer macrophages become infected with M. marinum due to reduced macrophage motility, favoring the contention of mycobacterial infection. (C) shows enhanced recruitment of macrophages to sites of infection due to an exacerbated Cxcr3.2 signaling because of higher ligand availability in absence of the scavenging function of Cxcr3.3. The dissemination of mycobacteria into these newly recruited macrophages will later seed secondary granulomas, supporting the dissemination of the infection.