Impact of E. muris infection on B. burgdorferi–induced joint pathology in mice

Tick-borne infections are increasing in the United States and around the world. The most common tick-borne disease in the United States is Lyme disease caused by infection with the spirochete <i>Borrelia burgdorferi</i> (<i>Bb</i>), and pathogenesis varies from subclinical to severe. <i>Bb</i> infection is transmitted by <i>Ixodes</i> ticks, which can carry multiple other microbial pathogens, including <i>Ehrlichia</i> species. To address how the simultaneous inoculation of a distinct pathogen impacted the course of <i>Bb</i>-induced disease, we used C57BL/6 (B6) mice which are susceptible to <i>Bb</i> infection but develop only mild joint pathology. While infection of B6 mice with <i>Bb</i> alone resulted in minimal inflammatory responses, mice co-infected with both <i>Bb</i> and the obligate intracellular pathogen <i>Ehrlichia muris</i> (<i>Em</i>) displayed hematologic changes, inflammatory cytokine production, and emergency myelopoiesis similar to what was observed in mice infected only with <i>Em</i>. Moreover, infection of B6 mice with <i>Bb</i> alone resulted in no detectable joint inflammation, whereas mice co-infected with both <i>Em</i> and <i>Bb</i> exhibited significant inflammation of the ankle joint. Our findings support the concept that co-infection with <i>Ehrlichia</i> can exacerbate inflammation, resulting in more severe <i>Bb</i>-induced disease.