Cell and Tissue Tropism of Brucella spp

Abstract

Brucella spp. are facultatively intracellular bacteria that can infect, survive, and multiply in various host cell types in vivo and/or in vitro. The genus Brucella has markedly expanded in recent years with the identification of novel species and hosts, which has revealed additional information about the cell and tissue tropism of these pathogens. Classically, Brucella spp. are considered to have tropism for organs that contain large populations of phagocytes such as lymph nodes, spleen, and liver, as well as for organs of the genital system, including the uterus, epididymis, testis, and placenta. However, experimental infections of several different cultured cell types indicate that Brucella may actually have a broader cell tropism than previously thought. Indeed, recent studies indicate that certain Brucella species in particular hosts may display a pantropic distribution in vivo. This review discusses the available knowledge on cell and tissue tropism of Brucella spp. in natural infections of various host species, as well as in experimental animal models and cultured cells.

Keywords: Brucella; macrophage; trophoblast; tropism.

FIG 1

Placentitis in a cow with intralesional Brucella abortus. (A) Neutrophilic and necrotizing placentitis with large colonies of B. abortus in a placentome from a cow experimentally infected as previously described (23). (B) Immunolabeling of Brucella sp. with a polyclonal primary antibody anti-Brucella sp. in trophoblasts of a bovine placenta from a naturally infected cow.

FIG 2

Mouse model of Brucella spp. infection. (A) Microgranuloma in the liver of a mouse experimentally infected with Brucella ovis. (B) Immunolabeling of intralesional Brucella sp. (brown) in a hepatic granuloma of an experimentally infected mouse. The mice in panels A and B were inoculated with 10⁶ CFU/mouse immunoprecipitate and sampled at 7 days postinfection.

FIG 3

Placentitis in a mouse with intralesional B. abortus. (A) Neutrophilic and necrotizing placentitis with large colonies of B. abortus. (B) Necrosis with neutrophilic infiltration in the junctional zone of the placenta with large extracellular aggregates of B. abortus (arrowhead). The pregnant mice in panels A and B were inoculated with10⁵ CFU/mice immunoprecipitate at the fifth day of gestation and sampled at 13 days after infection. (C) Immunolabeling of Brucella sp. (brown) in the decidua and junctional zone of the placenta from experimentally infected mice as previously described (81). (D) Immunolabeling of Brucella sp. (brown) in the yolk sac from experimentally infected mice as previously described (81).

FIG 4

Infection of macrophages with Brucella sp. (A) Mouse macrophage cell line (J774) infected with B. ovis expressing mCherry (red) at 24 h postinfection with a multiplicity of infection of 1:100. (B) Transmission electron micrograph demonstrating the intracellular localization of B. abortus in membrane-bound vacuoles in cultured bovine macrophages experimentally infected as previously described (142).

FIG 5

Mouse endothelial cells experimentally infected with B. ovis expressing mCherry (red) at 24 h postinfection with a multiplicity of infection of 1:1,000.

FIG 6

Distribution of Brucella canis in tissues of naturally infected neonatal dogs demonstrated by immunohistochemistry (3-amino-9-ethylcarbazole [AEC]; red chromogen) as previously described (37). (A) In intravascular erythrocytes. (B) In erythrocytes in a glomerulus. (C) In the small intestine. (D) In adipose tissue (adipocytes). (E) In the myocardium. (F) In the ependyma in the central nervous system.

FIG 7

Most important target organs in various host species for Brucella spp. The figure was created with BioRender.com.