CD36 homologs determine microbial resistance to the Lyme disease spirochete

Abstract

AbstractPattern recognition receptors sense pathogens in arthropods and mammals through distinct immune processes. Whether these molecules share a similar function and recognize the same microbe in evolutionarily distant species remain ill-defined. Here, we establish that the CD36 superfamily is required forBorrelia burgdorferiresistance in both the arthropod vector and humans. Using the blacklegged tickIxodes scapularisand an electronic health record-linked biobank, we demonstrate that CD36 members elicit immunity to the Lyme disease spirochete. In ticks, the CD36-like protein Croquemort recognizes lipids and initiates the immune deficiency and jun N-terminal kinase pathways againstB. burgdorferi. In humans, exome sequencing and clinical information reveal that individuals withCD36loss-of-function variants have increased prevalence of Lyme disease. Altogether, we discovered a conserved mechanism of anti-bacterial immunity.One Sentence SummaryLipid receptors belonging to the CD36 superfamily exhibit a shared immune function in both ticks and humans.