Hyperglycemia Results in Decreased Immune Cell Infiltration and Increased Viral Load in the Lung in a Mouse Model of Rsv Infection Publisher Pubmed



Khodakhah F¹ ; Tahamtan A^{2, 3} ; Marzban M¹ ; Shadab A¹ ; Tavakoliyaraki M⁴ ; Hashemi SM⁵ ; Mokhatriazad T¹ ; Nakstad B^{6, 7} ; Salimi V¹ Show Affiliations
Source: Cytokine Published:2021

Abstract

Respiratory Syncytial virus (RSV) infection is a feared disease in vulnerable populations with impaired immune responses. There is currently no vaccine against RSV and young children along with elderly people are at increased risk of severe or sometimes life-threatening RSV infection. Hyperglycemia with immunomodulatory patterns can impact on infectious disease outcomes and immune system responses in diabetic patients. Even though research continues to uncover the complex mechanisms underlying RSV immunopathogenesis and diabetes mellitus disease separately, limited information is available about interaction between these two phenomena. Here, we evaluated the influence of hyperglycemia as the hallmark of diabetes mellitus disease on the pathogenesis and immunopathogenesis of RSV in a mouse model. In this experiment, hyperglycemia was induced by intraperitoneal injection of Streptozotocin (STZ), and after diabetes confirmation, mice were infected with RSV-A2, and the immune responses were followed for 5 days until the mice were sacrificed. Analyses on airway immune cell influx, T-Lymphocyte subtypes, cytokines secretion, lung histopathology, and viral load were conducted. Our results showed that hyperglycemia resulted in reduced lung immune cells infiltration totally and it was associated with decreased pathological damage of the lung. Following RSV infection in hyperglycemic mice, the ratio of CD4/CD8 T-Lymphocytes due to CD8+ depletion, increased. Furthermore, the level of IFN-γ and IL-17A cytokines decreased, whereas IL-10 showed an upward trend and the viral load increased in hyperglycemic mice compared with normoglycemic mice. In conclusion, these findings indicate that hyperglycemia can ameliorate and downregulate RSV-induced inflammatory and antiviral responses, and result in increment of viral load. © 2021 Elsevier Ltd