AUTHOR=Gutiérrez-Jiménez Cristina , Mora-Cartín Ricardo , Altamirano-Silva Pamela , Chacón-Díaz Carlos , Chaves-Olarte Esteban , Moreno Edgardo , Barquero-Calvo Elías 

TITLE=Neutrophils as Trojan Horse Vehicles for Brucella abortus Macrophage Infection

JOURNAL=Frontiers in Immunology

VOLUME=Volume 10 - 2019

YEAR=2019

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2019.01012

DOI=10.3389/fimmu.2019.01012

ISSN=1664-3224

ABSTRACT=Brucella abortus is 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 phagocytosis of 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 phagocytosis mechanism. 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 “Trojan horse” vehicles for the efficient dispersion and replication of the bacterium within the host.