Prostaglandin E2 Production and T Cell Function in Mouse Adenovirus Type 1 Infection following Allogeneic Bone Marrow Transplantation

• Published in: PloS one Vol. 10; no. 9; p. e0139235
• Main Authors: McCarthy, Mary K, Procario, Megan C, Wilke, Carol A, Moore, Bethany B, Weinberg, Jason B
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 25.09.2015; Public Library of Science (PLoS)
• Subjects: Adenoviridae - physiology; Adenoviridae Infections - etiology; Adenoviridae Infections - pathology; Adenoviridae Infections - virology; Adenoviruses; Animals; Bacterial infections; Bone marrow; Bone marrow transplantation; Bone Marrow Transplantation - adverse effects; Bronchoalveolar Lavage Fluid - chemistry; CD8 antigen; Complications; Critical care; Cytokines - physiology; Cytotoxicity; Dinoprostone - analysis; Dinoprostone - biosynthesis; Drug dosages; Good Manufacturing Practice; Granzyme B; Immunology; Immunotherapy; Infections; Infectious diseases; Interleukin 17; Interleukin 2; Interleukin 4; Internal medicine; Lung - pathology; Lung - physiopathology; Lung - virology; Lungs; Lymphocytes; Lymphocytes B; Lymphocytes T; Male; Medicine; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Misoprostol; Mortality; Neutrophils; Pathogenesis; Pediatrics; Prostaglandin E2; Rodents; Stem cell transplantation; Stem cells; T-Lymphocytes - physiology; Transplantation; Transplants & implants; Viral infections; Viral Load; Viruses; β-Interferon; γ-Interferon; Ann Arbor Michigan; United States > US; Michigan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0139235

Adenovirus infections are important complications of bone marrow transplantation (BMT). We demonstrate delayed clearance of mouse adenovirus type 1 (MAV-1) from lungs of mice following allogeneic BMT. Virus-induced prostaglandin E2 (PGE2) production was greater in BMT mice than in untransplanted controls, but BMT using PGE2-deficient donors or recipients failed to improve viral clearance, and treatment of untransplanted mice with the PGE2 analog misoprostol did not affect virus clearance. Lymphocyte recruitment to the lungs was not significantly affected by BMT. Intracellular cytokine staining of lung lymphocytes demonstrated impaired production of INF-γ and granzyme B by cells from BMT mice, and production of IFN-γ, IL-2, IL-4, and IL-17 following ex vivo stimulation was impaired in lymphocytes obtained from lungs of BMT mice. Viral clearance was not delayed in untransplanted INF-γ-deficient mice, suggesting that delayed viral clearance in BMT mice was not a direct consequence of impaired IFN-γ production. However, lung viral loads were higher in untransplanted CD8-deficient mice than in controls, suggesting that delayed MAV-1 clearance in BMT mice is due to defective CD8 T cell function. We did not detect significant induction of IFN-β expression in lungs of BMT mice or untransplanted controls, and viral clearance was not delayed in untransplanted type I IFN-unresponsive mice. We conclude that PGE2 overproduction in BMT mice is not directly responsible for delayed viral clearance. PGE2-independent effects on CD8 T cell function likely contribute to the inability of BMT mice to clear MAV-1 from the lungs.