Inhibition of phagocytosis and pyroptosis of macrophages promotes Bartonella invasion into the bloodstream through lymphatic circulation

The hallmark of Bartonella infection is long-lasting intra-erythrocytic parasitism. However,the process of Bartonella bacteremia is still enigmatic. Here, we used Bartonella tribocorum (Bt) to understand how Bartonella invasion into the bloodstream from dermal inoculation might occur. Bartonella was poorly phagocytized by peritoneal macrophages in vitro. Intracellular Bartonella survived and replicated in macrophages at early stage of infection. Intracellular Bartonella inhibited spontaneous cell death of macrophage. Moreover, Bartonella inhibited Salmonella-induced pyroptosis and mildly reduced inflammasome activation through an unidentified mechanism. A rat model confirmed that Bartonella was also inadequately phagocytized in vivo, as numerous free-floating bacilli were observed in lymph collected from thoracic duct drainage as early as two hours post inoculation. Lymphatic fluid drainage into the bloodstream significantly reduced the bacterial load in the bloodstream. These findings illustrated a potential route that Bartonella invade blood stream from dermal inoculation before they are competent to infect erythrocytes. at Freie U nivrsitaet B erlin on N ovem er 3, 2016 http://jidrdjournals.org/ D ow nladed from