No abstract

Abstract. Canid herpesvirus 1 (CaHV-1) is a well-known cause of fatal hepatic and renal necrosis in neonatal puppies. In adult dogs infected with CaHV-1, papulovesicular genital lesions may be observed. CaHV-1 infection during pregnancy can lead to embryonic resorption, abortion, and stillbirth. In high-density dog populations, CaHV-1 can also contribute to kennel cough. Furthermore, recent literature has clearly documented that CaHV-1 can induce ocular disease in immature and adult dogs. The current study describes a case of fatal CaHV-1 infection in a 9-year-old spayed female Bichon Frise dog. Following a history of vomiting and diarrhea, the dog deteriorated and subsequently died. The main lesions were multifocal areas of necrosis with intranuclear inclusion bodies in the liver, adrenal gland, and small intestine, similar to the lesions observed in CaHV-1-infected puppies. Infection with CaHV-1 was confirmed on samples of liver by polymerase chain reaction, immunohistochemistry, and in situ hybridization. There was no indication of immunosuppression in this dog. Based on the results presented herein, CaHV-1 should be included in the list of differential diagnoses of hepatic necrosis in adult dogs.

Campylobacter jejuni is a leading cause of gastroenteritis that has been causally linked with development of the autoimmune peripheral neuropathy Guillain Barré Syndrome (GBS). Previously, we showed that C. jejuni isolates from human enteritis patients induced Type1/17-cytokine dependent colitis in interleukin-10 (IL-10) −/− mice, while isolates from GBS patients colonized these mice without colitis but instead induced autoantibodies that cross-reacted with the sialylated oligosaccharide motifs on the LOS of GBS-associated C. jejuni and the peripheral nerve gangliosides. We show here that infection of IL-10 −/− mice with the GBS but not the colitis isolate led to sciatic nerve inflammation and abnormal gait and hind limb movements, with character and timing consistent with this syndrome in humans. Autoantibody responses and associated nerve histologic changes were dependent on IL-4 production by CD4 T cells. We further show that Siglec-1 served as a central antigen presenting cell receptor mediating the uptake of the GBS isolates via interaction with the sialylated oligosaccharide motifs found specifically on the LOS of GBS-associated C. jejuni , and the ensuing T cell differentiation and autoantibody elicitation. Sialylated oligosaccharide motifs on the LOS of GBS-associated C. jejuni therefore acted as both the Siglec-1-ligand for phagocytosis, as well as the epitope for autoimmunity. Overall, we present a mouse model of an autoimmune disease induced directly by a bacterium that is dependent upon Siglec-1 and IL-4. We also demonstrate the negative regulatory role of IL-10 in C. jejuni induced autoimmunity and provide IL-4 and Siglec-1 blockade as potential therapeutic interventions against GBS.

Two of three captive adult African ostriches exhibited inappetance and weakness. In spite of treatment, the two birds were euthanized because of lack of clinical improvement. Postmortem examination demonstrated exocrine pancreatic degeneration, necrosis, and atrophy. Grossly, one ostrich had a markedly diminished pancreatic mass. Histologically, there was massive pancreatic acinar (exocrine) atrophy, marked interstitial fibrosis, and tubular complex formation in one animal, and the second ostrich had active pancreatic acinar necrosis. Toxicologic testing revealed markedly elevated liver zinc levels in the first two birds, whereas the third ostrich had normal serum levels of zinc and continues without apparent disease. This form of zinc toxicosis, while previously reported in different avian species, has been only rarely described in ratites.

Campylobacter jejuni is a leading cause of foodborne enteritis and has also been linked to the autoimmune neuropathy, Guillain Barré syndrome. IL-10−/− mice serve as C. jejuni colitis model, but a mouse model for GBS is lacking. Immune mechanisms responsible for C. jejuni mediated colitis, protection from colitis or initiation of autoimmune sequelae are also largely unknown. We demonstrate that IL-10−/− mice infected with colitogenic human isolates of C. jejuni had significantly upregulated Type1/17 but not Type2 cytokines in the colon coincident with infiltration of phagocytes, T cells and Innate Lymphoid Cells. Both ILCs and T cells participated in IFN-γ, IL-17 and IL-22 upregulation but in a time- and organ-specific manner. However, T cells were necessary for colitis. Furthermore, depleting IFN-γ, IL-17 or both significantly ameliorated colitis and drove the colonic responses towards Type2 cytokine and antibody induction. In contrast, C. jejuni GBS patient strains induced mild colitis associated with blunted Type 1/17 but enhanced Type2 responses. Moreover, IL-4 and CD4+ T cell dependent Type2 antibodies (but not the Type1/17 antibodies) elicited exclusively by the GBS strains cross-reacted with peripheral nerve antigens. This lead to macrophage mediated demyelination of sciatic nerves that manifested with gait ataxia and hind limb paraparesis in the IL-10-/- mice. Therefore, this is the first mouse model of an autoimmune disease induced directly by an enteric bacterium.