Interaction of Bartonella henselae with the murine macrophage cell line J774: Infection and proinflammatory response

Bartonella henselae is the causative agent of cat scratch disease (CSD), a self-limiting condition characterized by a subacute regional lymphadenopath y that may develop into disseminated bartonellosis in immunocompromised sub jects. Mice experimentally infected with B. henselae display typical liver and spleen granulomas rich in T cells and macrophages. So far there are no data on the interaction between bartonellae and macrophages. In order to cl arify this topic, we investigated the interaction of B. henselae with J774, a mouse macrophage cell line. Analysis of bacterial uptake by functional a ssays and transmission electron microscopy indicates that bartonellae can e nter and survive inside J774. Entry occurred within 30 min postinfection an d reached a plateau at 160 min. Infection of J774 was followed by a dose-de pendent release of the proinflammatory cytokines tumor necrosis factor alph a, interleukin 1 beta (IL-1 beta), and IL-6. Bartonellae persisted intracel lularly without loss of viability for at least 8 h, and their number slight ly decreased 24 h postinfection. Gamma interferon (IFN-gamma) treatment of J774 significantly decreased the number of recoverable bacteria at 8 and 24 h. This enhancement of macrophage bactericidal activity was associated wit h nitric oxide (NO) release and was prevented by the addition of the compet itive inhibitor of NO synthesis NG-monomethyl L-arginine. These findings su ggest that IFN-gamma -mediated activation of macrophages may be important f or the clearing of B. henselae infection and that anti-B. henselae microbic idal activity of IFN-gamma -activated macrophages is mediated to a large ex tent by NO production.