NETosis is a unique form of cell death that is characterized by the release of decondensed chromatin and granular contents to the extracellular space. The initial observation of NETosis placed the process within the context of the innate immune response to infections. Neutrophils, the most numerous leukocytes that arrive quickly at the site of an infection, were the first cell type shown to undergo extracellular trap formation. However, subsequent studies showed that other granulocytes are also capable of releasing nuclear chromatin following stimulation. The extracellular chromatin acts to immobilize microbes and prevent their dispersal in the host. Bacterial breakdown products and inflammatory stimuli induce NETosis and the release of NETs requires enzyme activities. Histones in NET chromatin become modified by peptidylarginine deiminase 4 (PAD4) and cleaved at specific sites by proteases. NETs serve for attachment of bactericidal enzymes including myeloperoxidase, leukocyte proteases, and the cathelicidin LL-37. While the benefit of NETs in an infection appears clear, NETs also figure prominently at the center of various pathologic states. Therefore, it is important for NETs to be efficiently cleared; else digestive enzymes may gain access to tissues where inflammation takes place. Persistent NET exposure at sites of inflammation may lead to a further complication: NET antigens may provoke acquired immune responses and, over time, could initiate autoimmune reactions. Recent studies identified aberrant NET synthesis and/or clearance in inflammatory/autoimmune conditions such as systemic lupus erythematosus (SLE), psoriasis, ANCA-positive vasculitis, gout and Felty’s syndrome. In the case of SLE, for example, it appears that LL-37 exposed in the NETs may be a significant trigger of type I Interferon responses in this disease. Recent evidence also implicates aberrant NET formation in the development of endothelial damage, atherosclerosis and thrombosis. NETosis is thus of interest to researchers who investigate innate immune responses, host-pathogen interactions, chronic inflammatory disorders, cell and vascular biology, biochemistry, and autoimmunity. As we approach the 10-year-anniversary of the initial discovery of NETosis, it is useful and timely to review the so far identified mechanisms and pathways of NET formation, their role in bacterial and fungal defense and their putative importance as inducers of autoimmune responses. We look forward to a rich and rigorous discussion of these and related issues that benefit from interdisciplinary approaches, collaborations and exciting discoveries.

This book is a printed edition of the Special Issue "Identification and Characterization of Antimicrobial Peptides with Therapeutic Potential" that was published in Pharmaceuticals

Amebiasis, a parasitic disease transmitted by the unicellular protozoan parasite Entamoeba histolytica, is the cause of at least 100,000 deaths each year. The disease is mostly prevalent in developing countries and is one of the three common causes of death from parasitic diseases. The parasite has two stages in its life cycle in the host: the infective cyst and the invasive trophozoite. In the large intestine, the parasite feeds on bacteria and on cellular debris. No vaccine against amebiasis currently exists. Although metronidazole is the drug of choice for treating amebiasis, adverse effects in patients and potential resistance to metronidazole in other protozoa exist. About nine out of 10 people who are infected with E. histolytica are asymptomatic and in those individuals who develop symptoms, bloody diarrhea (amebic colitis) and liver abscess are the most common symptoms. One possible explanation for this observation is the difference in the gut microbiota between individuals that may significantly influence the host’s immune response in amebiasis and E. histolytica's virulence. Amebiasis is characterized by acute inflammation of the intestine with release of pro-inflammatory cytokines, reactive oxygen species and reactive nitrogen species from activated cells of the host's immune system. In recent years, significant advances on the cell biology of Entamoeba infection have been achieved through the development of new genetic tools to manipulate gene expression in the parasite and through the application of Omics tools. In this Research Topic, we welcome high quality original research articles, as well as review, opinion or method articles, on amebiasis including but not limited to the regulation of gene expression, cell biology and signaling, adaptation and resistance to environmental stresses, metabolism, pathogenesis and immunity, pathogenesis and microbiome, drug discovery and drug resistance.