Mechanisms of humoral immunity during Ehrlichia chaffeensis infection.

Our laboratory has been investigating the mechanisms of host defense during Ehrlichia chaffeensis infection in the mouse. Although major roles are clearly played by T cells, we found that antibodies could also control infection in both normal and immunocompromised SCID mice, and could protect the latter from lethal infection. Antibodies are not generally effective during such intracellular infections, so we would like to understand exactly how antibodies can mediate immunity in this model. We have found that much of the humoral immune response is directed at the bacterial outer membrane proteins (OMPs), and that highly effective OMP antibodies (mostly IgG2a) exhibited picomolar affinities and very long binding half-lives. These antibodies, which could mediate bacterial clearance from tissues as early as 24 hours after administration, require host Fc receptors for their function(s). In contrast, we have failed to find any role for complement or reactive nitrogen intermediates, or for neutrophils, or for NK cells. One possible mechanism is that antibodies or immune complexes trigger microbiocidal activities in infected macrophages that lead to the elimination of bacteria residing inside host macrophages. Alternatively, it is proposed that antibodies opsonize bacteria exposed during intercellular transfer. This notion is supported by studies that have demonstrated the presence of bacteria in the extracellular milieu during infection, and suggests that our understanding of the behavior of the bacterium in the host may be key to our understanding of its susceptibility to antibody-mediated host defenses.