Neutrophils as Trojan Horse Vehicles for Brucella abortus Macrophage Infection

Brucella abortusis a stealthy intracellular bacterial pathogen of animals and humans. This bacterium promotes the premature cell death of neutrophils (PMN) and resists the killing action of these leukocytes. B. abortus-infected PMNs presented phosphatidylserine(PS) as “eat me” signal on the cell surface. This signal promoted direct contacts between PMNs and macrophages (Ms) and favored the phagocytosisof the infected dying PMNs. Once inside Ms, B. abortus replicated within Ms at significantly higher numbers than when Ms were infected with bacteria alone. The high levels of the regulatory IL-10 and the lower levels of proinflammatory TNF-α released by the B. abortus-PMN infected Ms, at the initial stages of the infection, suggested a non-phlogistic phagocytosismechanism. Thereafter, the levels of proinflammatory cytokines increased in the B. abortus-PMN-infected Ms. Still, the efficient bacterial replication proceeded, regardless of the cytokine levels and M type. Blockage of PS with Annexin V on the surface of B. abortus-infected PMNs hindered their contact with Ms and hampered the association, internalization, and replication of B. abortus within these cells. We propose that B. abortus infected PMNs serve as “ Trojanhorse” vehicles for the efficient dispersion and replication of the bacterium within the host.