This model suggests that besides Mincle-/- mice, future investigation with targeted blockage of TNFα- or FcγR1/FcγR4-mediated pathways will help define the interplay of TNFα/Mincle/FcγR signaling in the regulation of host-O. tsutsugamushi interactions and pathology of scrub typhus. Here, CLEC4E is linked to scrub typhus.