<i>Anaplasma phagocytophilum</i> invasin AipA interacts with CD13 to elicit Src kinase signaling that promotes infection

Diverse microbes engage CD13 to infect host cells. Yet invasin-CD13 interactions, the signaling they invoke for pathogen entry, and the relevance of CD13 to infection <i>in vivo</i> are underexplored. Dissecting these concepts would advance fundamental understanding of a convergently evolved infection strategy and could have translational benefits. <i>Anaplasma phagocytophilum</i> infects neutrophils to cause granulocytic anaplasmosis, an emerging disease for which there is no vaccine and few therapeutic options. We found that <i>A. phagocytophilum</i> uses its surface protein and recently identified protective immunogen, AipA, to bind CD13 to elicit Src kinase signaling, which is critical for infection. We elucidated the AipA CD13 binding domain, which CD13 region AipA engages, and established that CD13 is key for <i>A. phagocytophilum</i> infection in vivo. Disrupting the AipA-CD13 interaction could be utilized to prevent granulocytic anaplasmosis and offers a model that could be applied to protect against multiple infectious diseases.