Müller cells are the predominant glial cell type in the retina and have a unique anatomy, with processes that span the entire retinal thickness. Although extensive morphological and physiological studies of Müller glia have been performed, much less is known about their role in retinal innate immunity, specifically in infectious endophthalmitis. They were found to express Toll-like receptors (TLRs), a major family of pattern recognition receptors (PRRs) that mediate innate responses and provide an important mechanism by which Müller glia are able to sense both pathogen- and host-derived ligands in the vitreous and the retina. An increasing body of evidence suggests that TLR-signaling mediates beneficial effects in the retina via production of pro-inflammatory cytokines/chemokines, antimicrobial peptides and neuroprotective growth factors to restore tissue homeostasis. In this review, we discussed retinal innate immunity in general with emphasis on the role of Müller glia in initiating retinal innate defense.

Leishmania has developed an intricate relationship with its host, primarily cells of the monocyte/macrophage lineage, where it exploits and subverts the host immune system by either inducing immunosuppression or promoting proparasitic host factors to ensure its survival and growth in an otherwise harsh milieu (3). Hijacking of innate immune functions of macrophages by Leishmania appears to be a multifarious event, as macrophages have inherently evolved to defend the host against invading pathogens by a myriad of effectors rather than providing a favorable environment to the pathogen. The chief molecular mechanisms by which Leishmania is known to inhibit the activation of macrophages toward its own benefit include suppression of deadly antimicrobial free radicals such as nitric oxide (NO), faulty antigen presentation, selective induction and suppression of host cell apoptosis, inhibition of cytokine production and hence cytokine-inducible macrophage function, and activation of T cells (4-8). Leishmania has evolved sophisticated mechanisms to alter the physiological program and activation of adaptive immune responses of host cells by exploiting host cell signaling mechanisms such as the downregulation of Ca 2ϩ -dependent classical protein kinase C (PKC) activity and extracellular signal-regulated kinase (ERK) phosphorylation and activity (9, 10). Using mainly host tyrosine phosphatases, Leishmania is known to deactivate mitogen-activated protein kinases (MAPKs) in infected macrophages (5). Extensive manipulations of host cell effector (innate and adaptive) functions by pathogens must be reflected at the levels of transcripts as well as proteins. Enormous efforts made in the field of host gene expression profiling using different (murine and/or human) cell types and different species of Leishmania provide key insights into an extensive modulation of gene function and contribute to a better understanding of the dynamics of gene expres-

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Leishmania is an obligate intracellular parasite that replicates inside phagolysosomes or parasitophorous vacuoles (PV) of the monocyte/macrophage lineage. It reprograms macrophages and produces a metabolic state conducive to successful infection and multiplication. MicroRNAs (miRNAs), a class of small 22 to 24 nucleotide noncoding regulatory RNAs alter the gene expression and consequently proteome output by targeting mRNAs, may play a regulatory role in modulating host cell functions. In the present study, we demonstrate the novel regulatory role of host microRNA, MIR30A-3p in modulation of host cell macroautophagy/autophagy after infection with L. donovani. Our in vitro studies showed that MIR30A-3p expression was significantly enhanced after L. donovani infection in a time-dependent manner. Transient transfection with a MIR30A-3p inhibitor followed by L. donovani infection promoted the autophagic response and decreased the intracellular parasite burden in both THP-1 cells and human monocytederived macrophages (HsMDM). BECN1/Beclin 1, the mammalian ortholog of yeast Vps30/Atg6, is a key autophagy-promoting protein that plays a key role in the regulation of cell death and survival. We report BECN1-dependent modulation of host cell autophagy in response to L. donovani infection. Pretreatment of L. donovani-infected macrophages with the MIR30A-3p mimic decreased and with antagomir increased the expression of BECN1 protein. We demonstrate that BECN1 is a potential target of MIR30A-3p and this miRNA negatively regulates BECN1 expression. Our present study reveals for the first time a novel role of MIR30A-3p in regulating autophagy-mediated L. donovani elimination by targeting BECN1. The present study has significant impact for the treatment of visceral leishmaniasis.