Anti-Non-Bilayer Phospholipid Arrangement Antibodies Trigger an Autoimmune Disease Similar to Systemic Lupus Erythematosus in Mice

Anti-lipid antibodies are present in some infectious and autoimmune diseases, such as Systemic Lupus Erythematosus (SLE). Particularly, anti-non-bilayer phospholipid arrangement (NPA) antibodies have been detected in patients with SLE, and these antibodies trigger a disease similar to human lupus in mice. NPA are lipid associations different from the lipid bilayer of cellular membranes and, since they are transient, they are not immunogenic. However, if NPA are stabilized by drugs, they induce an immune response with the production of anti-NPA antibodies, which bind to NPA on cell membranes and generate cell lysis. As a result, intracellular antigens are exposed and trigger an immune response that generates more auto-antibodies. In this chapter, we describe the formation and stabilization of NPA, the induction of B cell responses to generate anti-NPA antibodies, and the characteristics that the disease caused by these antibodies in mice shares with human lupus

The Role of Lipopeptidophosphoglycan in the Immune Response to Entamoeba histolytica

The sensing of Pathogen Associated Molecular Patterns (PAMPs) by innate immune receptors, such as Toll-like receptors (TLRs), is the first step in the inflammatory response to pathogens. Entamoeba histolytica, the etiological agent of amebiasis, has a surface molecule with the characteristics of a PAMP. This molecule, which was termed lipopeptidophosphoglycan (LPPG), is recognized through TLR2 and TLR4 and leads to the release of cytokines from human monocytes, macrophages, and dendritic cells; LPPG-activated dendritic cells have increased expression of costimulatory molecules. LPPG activates NKT cells in a CD1d-dependent manner, and this interaction limits amebic liver abscess development. LPPG also induces antibody production, and anti-LPPG antibodies prevent disease development in animal models of amebiasis. Because LPPG is recognized by both the innate and the adaptive immune system (it is a “Pamptigen”), it may be a good candidate to develop a vaccine against E. histolytica infection and an effective adjuvant

Development of Novel Drugs for the Treatment of Chagas Disease

Chagas disease, or American trypanosomiasis, is a zoonosis caused by the hemoflagellate parasite Trypanosoma cruzi. It is mainly transmitted by the bite of blood-sucking insects. It is endemic in Latin America and emerging in the rest of the world, affecting approximately six million people. The drugs Benznidazole and Nifurtimox currently used for its treatment are not totally effective in the chronic phase of the disease. In addition, they are toxic, and there are many resistant Trigonoscuta cruzi strains. Therefore, developing new drugs for the treatment of Chagas disease is necessary. This chapter describes the development of drugs that inhibit α-hydroxy acid dehydrogenase isoenzyme II, a key enzyme in parasite energy metabolism. These drugs have shown more significant trypanocidal activity than the currently used drugs, and they have also prevented the development of chronic Chagas disease in infected mice

Therapeutic Properties of <em>Trichinella spiralis</em> (Nematoda) in Chronic Degenerative Diseases

Diseases produced by helminth parasites occur frequently in underdeveloped countries where they present a serious public health problem. At the same time, in these regions, a lower rate of autoimmune and allergic diseases has been observed. Due to these observations, some researchers have proposed that some helminths, such as Trichinella spiralis or its proteins, have strong anti-inflammatory potential, or have assessed them as modulating agents of the immune response. T. spiralis shifts the host immune response from a Th1 profile, characterized by pro-inflammatory cytokines, to a Th2 profile, characterized by the release of different cytokines with anti-inflammatory properties. This parasite has shown high therapeutic potential in a wide variety of disease models. In one of the most promising, the experimental lupus model in mice, the release of anti-inflammatory cytokines IL-4 and IL-10 and delayed onset of the key clinical features of the experimental lupus model for at least 5 months were observed, when previously parasitized. This is the first study to date that focuses on the use of T. spiralis as an immunomodulator in lupus disease. In conclusion, further study of the immune response generated by the parasite is necessary to advance the development of new therapies for inflammatory diseases

Molecular and Microbial Microenvironments in Chronically Diseased Lungs Associated with Cystic Fibrosis.

To visualize the personalized distributions of pathogens and chemical environments, including microbial metabolites, pharmaceuticals, and their metabolic products, within and between human lungs afflicted with cystic fibrosis (CF), we generated three-dimensional (3D) microbiome and metabolome maps of six explanted lungs from three cystic fibrosis patients. These 3D spatial maps revealed that the chemical environments differ between patients and within the lungs of each patient. Although the microbial ecosystems of the patients were defined by the dominant pathogen, their chemical diversity was not. Additionally, the chemical diversity between locales in the lungs of the same individual sometimes exceeded interindividual variation. Thus, the chemistry and microbiome of the explanted lungs appear to be not only personalized but also regiospecific. Previously undescribed analogs of microbial quinolones and antibiotic metabolites were also detected. Furthermore, mapping the chemical and microbial distributions allowed visualization of microbial community interactions, such as increased production of quorum sensing quinolones in locations where Pseudomonas was in contact with Staphylococcus and Granulicatella, consistent with in vitro observations of bacteria isolated from these patients. Visualization of microbe-metabolite associations within a host organ in early-stage CF disease in animal models will help elucidate the complex interplay between the presence of a given microbial structure, antibiotics, metabolism of antibiotics, microbial virulence factors, and host responses.IMPORTANCE Microbial infections are now recognized to be polymicrobial and personalized in nature. Comprehensive analysis and understanding of the factors underlying the polymicrobial and personalized nature of infections remain limited, especially in the context of the host. By visualizing microbiomes and metabolomes of diseased human lungs, we reveal how different the chemical environments are between hosts that are dominated by the same pathogen and how community interactions shape the chemical environment or vice versa. We highlight that three-dimensional organ mapping methods represent hypothesis-building tools that allow us to design mechanistic studies aimed at addressing microbial responses to other microbes, the host, and pharmaceutical drugs

Efectividad de la suspensión bacteriana sublingual en la prevención de infecciones de vías aéreas de repetición en pediatría

Antecedentes: Las infecciones de vías aéreas superiores (IVASR) son muy frecuentes en la población pediátrica. La mayoría de estas infecciones son leves, pero por la cronicidad afectan la calidad de vida (CdV), además de elevados costos por la atención médica. El uso de extractos bacterianos (EB) que estimulen la inmunidad general pueden reducir su frecuencia y mejorar la CdV del paciente. Objetivo: Evaluar la efectividad de un EB en la prevención de IVASR en niños de 1 a 6 años. Métodos: Se aleatorizaron niños entre 1 y 6 años, con diagnóstico IVASR en 3 grupos distintos, seguimiento médico a las 6 y 12 semanas tras el inicio. El EB se administró con dosis distintas a cada grupo. Se utiliza una prueba de ANOVA con un post hoc Tukey para comparaciones múltiples (error tipo I máximo de 0.05). Resultados: Se incluyeron 33 niños (12 niñas) con una media de edad de 3.11 años. La frecuencia de IVASR previo al tratamiento en promedio fue de 2.2 eventos/mes y de 0.9 y de 0.4 eventos/mes a las 6 y 12 semanas respectivamente. La IVARS se redujeron un 76.9% a los 3 meses de tratamiento. (Gráfica). No se reportaron efectos adversos. Conclusiones: El EB es seguro y efectivo en disminuir la frecuencia de IVASR en niños en concordancia con la literatura. No hay suficiente evidencia científica publicada pero el EB parece tener aplicación en la prevención y tratamiento de las IVASR. La administración sublingual es cómoda en este grupo etario 

The histone deacetylase inhibitor valproic acid attenuates phospholipase Cγ2 and IgE-mediated mast cell activation.

Mast cell activation through the high-affinity IgE receptor (FcεRI) plays a central role in allergic reactions. FcεRI-mediated activation triggers multiple signaling pathways leading to degranulation and synthesis of different inflammatory mediators. IgE-mediated mast cell activation can be modulated by different molecules, including several drugs. Herein, we investigated the immunomodulatory activity of the histone deacetylase inhibitor valproic acid (VPA) on IgE-mediated mast cell activation. To this end, bone marrow-derived mast cells (BMMC) were sensitized with IgE and treated with VPA followed by FcεRI cross-linking. The results indicated that VPA reduced mast cell IgE-dependent degranulation and cytokine release. VPA also induced a significant reduction in the cell surface expression of FcεRI and CD117, but not other mast cell surface molecules. Interestingly, VPA treatment inhibited the phosphorylation of PLCγ2, a key signaling molecule involved in IgE-mediated degranulation and cytokine secretion. However, VPA did not affect the phosphorylation of other key components of the FcεRI signaling pathway, such as Syk, Akt, ERK1/2, or p38. Altogether, our data demonstrate that VPA affects PLCγ2 phosphorylation, which in turn decreases IgE-mediated mast cell activation. These results suggest that VPA might be a key modulator of allergic reactions and might be a promising therapeutic candidate