Actin is a major cytoskeletal element involved in multiple cellular processes. Actin‐rich regions present along the neuronal process aid in neuronal function, mediating multiple events involved in organelle trafficking. Actin is involved in organelle biogenesis, transport, and anchoring at specific locations. These functions can potentially be regulated by actin in a myosin‐dependent or myosin‐independent manner. The actin network could aid in membrane remodeling through membrane constriction, motor dependent transport, polymerization‐based transport, cargo anchoring, and halting of cargo by acting as a physical barrier. Additionally, actin dynamics is perturbed in some neurodegenerative diseases where it could impact organelle biogenesis, transport, or anchoring thereby contributing to progression of disease phenotypes. The role of actin and myosin in organelle trafficking is the primary focus of this review.
In this study, we investigated the response of myeloid-derived suppressor cells (MDSCs) during the pathogenesis of an immunoblinding disease of the cornea caused by HSV type 1 infection. We also measured the anti-inflammatory potential of in vitro–differentiated MDSCs in dampening herpetic stromal keratitis resulting from primary ocular HSV1 infection in mice. In the lymphoid organs and inflamed corneal tissues, MDSCs were phenotypically characterized as CD11b+Gr1lo-int cells. Sorted CD11b+Gr1lo-int cells, but not CD11b+Gr1hi cells, suppressed the proliferation and cytokine production by stimulated CD4+ T cells. In vitro–generated MDSCs inhibited the activity of stimulated CD4+ T cells in a predominantly contact-dependent manner. An adoptive transfer of in vitro–generated MDSCs before or after ocular HSV1 infection controlled herpetic stromal keratitis lesions. The transferred MDSCs were primarily recovered from the lymphoid organs of recipients. Surprisingly, MDSCs recipients expanded their endogenous Foxp3+ regulatory T cells (Tregs). We further demonstrated the MDSCs mediated stabilization of Foxp3 expression in already differentiated Tregs and their ability to cause an efficient de novo conversion of Foxp3+ Tregs from stimulated Foxp3−CD4+ T cells. These effects occurred independent of TGF-β signaling. Therefore, the therapeutic potential of MDSCs could be harnessed as a multipronged strategy to confer an infectious tolerance to the host by activating endogenous regulatory mechanisms.
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