Neurobrucellosis (Brucella ceti) in striped dolphins (Stenella coeruleoalba): Immunohistochemical studies on immune response and neuroinflammation

Abstract

Neurobrucellosis is a shared condition of cetaceans and humans. However, the pathogenesis and immune response in cetacean neurobrucellosis has not been extensively studied. In this multicentric investigation, 21 striped dolphin (Stenella coeruleoalba) neurobrucellosis (Brucella ceti) cases diagnosed over a 10-year period (2012-2022) were retrospectively evaluated. For each case, morphological changes were assessed by evaluating 21 histological parameters. Furthermore, the immunohistochemical expression of Brucella antigen, glial fibrillary acid protein (GFAP), and a selection of inflammatory cell (IBA-1, CD3, and CD20) and cytokine (tumor necrosis factor-alpha [TNF-α], interferon-gamma [IFN-γ], interleukin [IL]-1β, IL-2, and IL-6) markers were investigated. Inflammation of the leptomeninges, ependyma, and/or choroid plexus was lymphohistiocytic, containing macrophages/microglia (IBA-1+), T-cells (CD3+), and B-cells (CD20+) in equal proportion. B-cells occasionally formed tertiary follicles. GFAP expression showed astrocytosis in most cases. Expression of TNF-α, IFN-γ, and IL-2 indicated an intense proinflammatory response, stimulating both macrophages and T-cells. Our results showed that the inflammation and neuroinflammation in neurobrucellosis of striped dolphins mimic human neurobrucellosis and in vitro and in vivo studies in laboratory animals. Cetacean disease surveillance can be exploited to expand the knowledge of the pathogenesis and immunology of infectious diseases, particularly brucellosis, under a One Health approach.