Original Investigation into the Molecular Mechanisms of Glucocorticoid-Induced Immunosuppression in Cattle Infected with Foot-and-Mouth Disease Virus in Plateau State, North Central Nigeria

The immunosuppressive axis activated by glucocorticoids during foot-and-mouth disease virus infection has been proposed as a mechanism that facilitates viral persistence in cattle, but the molecular evidence for this pathway in Nigerian Zebu populations is absent from the current literature. This doctoral study made original contributions by investigating the molecular mechanisms of glucocorticoid-induced immunosuppression in naturally infected Zebu cattle during a foot-and-mouth disease outbreak in Plateau State, North Central Nigeria. Eighty cattle were enrolled, with blood and nasal swabs collected at the onset of clinical signs, at seventy-two hours, and at days seven and fourteen of infection. Serum cortisol, adrenocorticotropic hormone, glucocorticoid receptor expression in peripheral blood mononuclear cells, interleukin-2, interleukin-4, interferon-gamma, and regulatory T-cell frequency were quantified by combined immunoassay and flow cytometry. A significant and sustained elevation in cortisol was confirmed throughout the acute infection phase. Glucocorticoid receptor expression in peripheral blood mononuclear cells was upregulated threefold at day three and positively correlated with suppression of interleukin-2 and interferon-gamma. Regulatory T-cell frequency expanded in proportion to cortisol elevation, with the highest regulatory T-cell proportions in animals with prolonged viral shedding. Mechanistic pathway modelling confirmed glucocorticoid receptor activation as the primary upstream driver of lymphocyte function depression. These original molecular findings contribute substantially to understanding immune evasion mechanisms in foot-and-mouth disease and have implications for vaccine adjuvant design in North Central Nigeria. Keywords: glucocorticoid, immunosuppression, foot-and-mouth disease, cortisol, Plateau State.