InVivoMAb anti-rat Kappa Immunoglobulin Light Chain

Neutrophils have been reported to have protective and detrimental functions in viral infections. However, the role of neutrophils remains unexplored in Japanese encephalitis virus (JEV) infection. In this study, we elucidated the dynamics of neutrophils and their influence on immune cell recruitment in subclinical and severe encephalitis in mouse models. Further, we depleted neutrophils from 3-4 week-old C57BL/6 mice using mAb1A8 (anti-Ly6G) antibody and studied their association with inflammation, viral replication, immune cell infiltration and disease outcome. We observed that an increase in JEV replication is associated with increased infiltration of neutrophils in the spleen and brain. Further studies confirmed that depletion of neutrophils at an early stage of JEV infection reduced CD8 abundance in the infected brain and accelerated death in mice. We also observed that inhibition of the CXCL12-CXCR4 signalling axis by antagonist AMD3100 reduced CD8 abundance in the brain and augmented inflammasome activation, leading to fatal encephalitis. Reduced CXCR4 levels in the spleen and blood of CD8+T cells correlated with enhanced Granzyme B level, indicating CD8 cells differentiated more into effector phenotypes in neutrophil-depleted mice. Furthermore, CD8 depletion delayed the death of mice infected with a sublethal strain compared to neutrophil-depleted mice, suggesting that neutrophils play a vital role in the early restriction of viral replication, whereas CD8 is essential later in clearing the virus. Taken together, our study sheds new light on the role of neutrophils in the pathogenic mechanisms of JEV encephalitis and highlights the importance of neutrophils and CD8 cells associated with disease outcomes.

Infection-associated thymic atrophy is common and results in T-cell imbalance and immune dysfunction. Severe dengue, caused by infection with the dengue virus (DV), is associated with perturbation of T cell functions. However, it is unclear whether perturbation of T cell functions is linked to changes in thymic function during dengue infection.

The microbiome is increasingly recognized as playing a critical role in lung cancer prevention, diagnosis, and treatment. While bacteria are essential for tumor angiogenesis, the impact of fungi on this process remains largely unexplored. In this study, we investigate effects of Aspergillus fumigatus (A. fumigatus) on lung cancer. We show that inhalation of A. fumigatus increases tumor burden and angiogenesis in mouse models. Interestingly, A. fumigatus does not directly affect the proangiogenic abilities of tumor cells or endothelial cells. Instead, A. fumigatus promotes the accumulation of myeloid-derived suppressor cells (MDSCs), particularly G-MDSCs, in tumor tissues. A. fumigatus increases VEGF-A secretion from tumor-associated MDSCs, promoting tumor angiogenesis. Furthermore, we identify solute carrier family 7 member 11 (SLC7A11) as a key player in regulating this proangiogenic function through an interaction with High Mobility Group Box 1 (HMGB1) in MDSCs. Our results shed light on the mechanisms by which A. fumigatus influences MDSCs to promote angiogenesis and demonstrate that commensal fungi influence host immunity and support tumor progression.