Kinetics of Placental Infection by Different Smooth Brucella Strains in Mice

Abstract

Abortion and reproductive failures induced by Brucella are the main symptoms of animal brucellosis. Laboratory animal models are essential tools of research to study the Brucella pathogenesis before experimentation in natural hosts. To extend the existing knowledge, we studied B. melitensis 16M (virulent) and Rev1 (attenuated) as well as B. suis bv2 infections in pregnant mice. Here, we report new information about kinetics of infection (in spleens, blood, placentas, vaginal shedding, and foetuses), serum cytokine profiles, and histopathological features in placentas and the litter throughout mice pregnancy. Both B. melitensis strains showed a marked placental tropism and reduced viability of pups (mainly in 16M infections), which was preceded by an intense Th1-immune response during placental development. In contrast, B. suis bv2 displayed lower placental tropism, mild proinflammatory immune response, and scarce bacterial transmission to the litter, thus allowing foetal viability. Overall, our studies revealed three different smooth Brucella patterns of placental and foetal pathogenesis in mice, providing a useful animal model for experimental brucellosis.

Brucella melitensis Wzm/Wzt System: Changes in the Bacterial Envelope Lead to Improved Rev1Δwzm Vaccine Properties

“…Histologically, Rev1 wzm enabled normal placentas with minimal neutrophilic infiltration and normal fetus viability, differing from Rev1 by its marked macroscopic edema, destruction of placental epithelium, and leukocyte infiltration in yolk sac. This mouse model has been successfully used as screening of pathogenicity (Grilló et al, 2012;Poveda-Urkixo et al, 2022), indicating that Rev1 wzm might be safer than Rev1 in pregnant animals and justifying further experiments in the natural host.…”

“…Bacterial adhesion, internalization, and intracellular multiplication in the BeWo (ATCC CCL-98; Sigma-Aldrich, San Luis, MO, United States) trophoblast-like cell line were determined as described previously (Castañeda-Roldán et al, 2004;Salcedo et al, 2013;Poveda-Urkixo et al, 2022). Briefly, 5 × 10 4 cells/well were cultured in 12-well microtiter plates (Sarstedt) with an enriched F-12K medium (Kaighn's Modification) supplemented with 10% of inactivated FBS and 2-mM L-glutamine (Glutamax 100×) (Gibco).…”

Characterization of Brucella abortus Mutant A19mut2, a Potential DIVA Vaccine Candidate with a Modification on Lipopolysaccharide

“…Histopathological examination of spleens and livers from mice inoculated with A19, A19mut2, or PBS was completed by Wuhan Servicebio Co., Ltd. (Wuhan, China) as previously described [ 13 ]. Briefly, the samples were fixed by 4% paraformaldehyde in properly fixed condition, and then trimmed, dehydrated, embedded, sectioned, stained by hematoxylin and eosin, sealed, and finally microscopically qualified.…”

Immune Responses Potentially Involved in the Gestational Complications of Brucella Infection

“…Since the early studies by Payne [56,57] until the present, different animal models have been tested to explain the pathology of abortion linked to Brucella infections, which allowed for reaching a consensus regarding the histopathological findings in the placentas of the different animal species. The most frequent lesions include placentitis, inflammatory infiltrates (including polymorphonuclear cells, lymphocytes, and macrophages), vasculitis, necrosis, and ulcerated or compromised chorioallantoic membrane [58][59][60][61][62][63][64][65][66]. Other more sporadic findings are placental calcifications (associated with chronicity), purulent or fibrinous exudates, granulomas, and placental edema.…”