Mast Cell Activation Triggered by Retrovirus Promotes Acute Viral Infection.

Mast cells (MCs) are strategically located at the host-environment interface and their non-allergic roles in the immune-surveillance of pathogens have recently gained more attention. However, MC-caused detrimental regulation of immune inflammations can promote viral invasion. Currently, the role of MCs in retroviral infection remains elusive. We have recently proved that human gut MCs could capture and transfer HIV-1 to CD4+ T cells for promoting viral spread; MC-released histamine augments HIV-1-induced functional polarization of dendritic cells to cause immunosuppression via stimulating the differentiation of regulatory T cells. In this study, we used a murine model of MuLV/Friend virus infection to address MC role in acute retroviral infection in vivo. The acute infection of MuLV/Friend virus could be established in C57BL/6 wild type mice, but viral acquisition showed low efficiency in C57BL/6-Kit W - sh/W - sh (Sash) mice which lack MCs. In mechanism, we found that MuLV/Friend virus triggered MC activation for degranulation; MC degranulation subsequently activated the granulocyte-like myeloid derived suppressive cells (G-MDSCs) to inhibit CD8+ T cells- and NK cells-mediated antiviral immune responses. The reconstruction of MCs in Sash mice promoted acute retroviral infection by regulating G-MDSCs functions and antiviral immune responses. Importantly, the administration of MC stabilizers to block cell degranulation elevated antiviral immune response and consequently suppressed retrovirus infection. This study uncovers a specific role of MCs in acute retroviral infection and elucidates the underlying immune-mechanisms. Targeting MCs may provide a novel approach for controlling acute infection by retroviruses.

Clinical application of different operative approach of total knee replacement in knee valgus patients. Retrospective cohort study.

PURPOSE: According to the severity of knee valgus, different operative approaches were applied in total knee replacement. Hence, we assessed the safety and efficacy of different operative approaches in the level IV study. METHODS: From May 2011 to March 2014, a retrospectively analysis was conducted among 31 patients with knee valgus (mild in 10 cases, moderate in 8 cases and severe in 13 cases based on Keblish grade). Medial approach trip knee replacement was performed in mild and moderate patients, which were assigned as medial approach group. Lateral approach was performed in severe patients, which was assigned as lateral approach group. Relevant results were compared between medial approach group and lateral approach group, including valgus corrected angle, postoperative knee joint activity and Kss score. Furthermore, operative time, postoperative blood loss, patellar trajectory and anterior knee pain were also compared between the two groups. RESULTS: All operations were successful without obvious complications. In medial approach group, postoperative knee valgus angle was (7 ±â€¯1)°. Three months after operation, degree of knee joint activity was (85.2 ±â€¯5.2)°, and KSS score of knee joint was (80.1 ±â€¯5.2). Significant differences were detected in these compared with preoperative data (all P < .05). Moreover, similar results were found in lateral approach group with postoperative knee valgus angle as (8.2 ±â€¯2.3)°, degree of knee joint activity three months after operation as (85.2 ±â€¯5.3)°, and KSS score of knee joint as (80.3 ±â€¯3.2). However, no significant differences were found among these three groups in operative time, postoperative blood loss, patellar trajectory or anterior knee pain. CONCLUSIONS: Different operative approaches in total knee replacement according to the severity of knee valgus were proved as effective and safe procedures, which deserved further application.