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Effect of Histophilus somni on Heart and Brain Microvascular Endothelial Cells
D O'Toole1, R Hunter2, T Allen1,3
11 Wyoming State Veterinary Laboratory, University of Wyoming, Laramie, WY, USA.
Abstract:
Histophilus somni is a pathogenic gram-negative bacterium responsible for pneumonia and septicemia in cattle. Sequelae include infectious thrombotic meningoencephalitis (ITME), myocarditis, arthritis, and abortion. These syndromes are associated with widespread vasculitis and thrombosis, implicating a role for endothelium in pathogenesis. Histopathologic and immunohistochemical investigation of 10 natural cases of bovine H. somni myocarditis and 1 case of ITME revealed intravascular H. somni in large biofilm-like aggregates adherent to the luminal surface of microvascular endothelium. Ultrastructurally, bacterial communities were extracellular and closely associated with degenerating or contracted endothelial cells. Histophilus somni was identified by bacterial culture and/or immunohistochemistry. Western blots of the bacterial isolates revealed that they expressed the immunodominant protective 40 kDa OMP and immunoglobulin-binding protein A (IbpA) antigens. The latter is a large surface antigen and shed fibrillar antigen with multiple domains. The cytotoxic DR2Fic domain of IbpA was conserved as demonstrated by polymerase chain reaction. Treatment of endothelial cells in vitro with IbpA in crude culture supernatants or purified recombinant GST-IbpA DR2Fic (rDR2) cytotoxin induced retraction of cultured bovine brain microvascular endothelial cells. By contrast, no retraction of bovine endothelium was induced by mutant rDR2H/A with an inactive Fic motif or by a GST control, indicating that the cytotoxic DR2Fic motif plays an important role in endothelial cell retraction in vasculitis. The formation of biofilm-like aggregates by H. somni on bovine microvascular endothelium may be fundamental to its pathogenesis in heart and brain.
Insights
Histophilus somni forms biofilm-like aggregates on bovine endothelium, contributing to vasculitis and severe diseases like myocarditis and meningoencephalitis. The bacterium
Area of Science:
- Veterinary microbiology
- Bacterial pathogenesis
- Bovine infectious diseases
Background:
- Histophilus somni causes significant diseases in cattle, including pneumonia, septicemia, myocarditis, and infectious thrombotic meningoencephalitis (ITME).
- These conditions involve vasculitis and thrombosis, suggesting endothelial cell involvement in the disease process.
- Understanding the interaction between H. somni and bovine endothelium is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the adherence and pathogenic mechanisms of Histophilus somni on bovine microvascular endothelium.
- To identify bacterial factors involved in endothelial cell damage and vasculitis.
- To elucidate the role of immunoglobulin-binding protein A (IbpA) in H. somni pathogenesis.
Main Methods:
- Histopathological and immunohistochemical analysis of natural bovine H. somni infection cases.
- Bacterial culture and Western blot analysis to identify expressed antigens.
- In vitro experiments using cultured bovine brain microvascular endothelial cells treated with bacterial components, including recombinant IbpA variants.
Main Results:
- Histophilus somni was observed in biofilm-like aggregates attached to the luminal surface of microvascular endothelium in affected cattle.
- Bacterial isolates expressed the 40 kDa OMP and immunoglobulin-binding protein A (IbpA) antigens.
- The cytotoxic DR2Fic domain of IbpA induced retraction of cultured bovine endothelial cells, while inactive mutants did not.
Conclusions:
- Histophilus somni forms biofilm-like aggregates on bovine endothelium, which is fundamental to its pathogenesis in heart and brain.
- The cytotoxic DR2Fic domain of IbpA is a key factor in H. somni-induced endothelial cell retraction and vasculitis.
- Targeting IbpA may offer a strategy for controlling H. somni infections in cattle.
