In the early phase of infections, enhancing cis association of Gal-9/Tim-3 ensures an appropriate TLR signaling in M/MФ that facilitate proper adaptive immune responses to successfully clear an acute infection; whereas some persistent pathogens such as HCV or HIV may enhance trans association of Gal-9/Tim-3 by up-regulating Gal-9 serum level and/or Tim-3 cell surface expression [45–48], and thus inhibit innate to adaptive immune responses and favor chronic infection. The gene discussed is HAVCR2; the disease is infection.