Preliminary characterization of the early immune response elicited by FMDV A/Arg/01 variants exhibiting differential pathogenesis in adult mice

KELLY, J.M.; CACCIABUE, M.; AÓN BERTOLINO, M.L.; GISMONDI, M.I.

Buenos Aires

Congreso; 2021 Meeting of the Global Foot-and-mouth Disease Research Alliance; 2021

Global Foot-and-mouth Disease Research Alliance (GFRA)

Two FMDV A/Arg/01 variants have been characterized previously in terms of pathogenicity in adult mice: the A01L variant is lethal 24-48 h after intraperitoneal inoculation (hpi), whereas the A01NL variant only produces mild signs of disease, independently of the dose used. Moreover, A01L reaches significantly higher viral load than A01NL in plasma and tissues at 22 hpi. Our aim was to compare the immune infiltrate and to study the induction of the innate immune response in tissues of mice inoculated with A01L and A01NL during the acute phase of infection.Formalin-fixed paraffin-embedded sections of pancreas from adult C57BL/6 mice taken at 14 and 22 hpi (A01L and A01NL), and at 72 hpi and 7 days pi (A01NL) (n=3 per group) were stained with hematoxylin and eosin and histopathological findings were recorded. The volume of the inflammatory infiltrate was estimated from digital images by counting the number of immune cells in a 75000 μm2-area/animal with ImageJ software. A dense polymorphonuclear infiltrate was evident in pancreas of mice inoculated with A01NL starting at 14 hpi and increasing throughout the evaluation period. At 7 dpi, the infiltrate was predominantly lymphoplasmacytic, suggesting the onset of the adaptive immune response. In turn, A01L-infected mice showed less immune infiltration in pancreas along with extended and diffuse fat necrosis.To evaluate the type I-interferon response elicited by A01L and A01NL infection, relative expression of interferon β (IFN-β) and IFN-stimulated genes (Mx1, OAS1a, PKR, and Viperin) was assessed by RT-qPCR in spleens of mice at 22 hpi. A significant up-regulation of IFN-β (p