Astrocytes derived from neural progenitor cells are susceptible to Zika virus infection.

Zika virus (ZIKV) was first isolated in 1947. From its isolation until 2007, symptoms of ZIKV-caused disease were limited (e.g., fever, hives, and headache); however, during the epidemic in Brazil in 2014, ZIKV infection caused Guillain-Barré syndrome in adults and microcephaly in fetuses and infants of women infected during pregnancy. The neurovirulence of ZIKV has been studied using neural progenitor cells (NPCs), brain organoids, neurons, and astrocytes. NPCs and astrocytes appear to be the most susceptible cells of the Central Nervous System to ZIKV infection. In this work, we aimed to develop a culture of astrocytes derived from a human NPC cell line. We analyze how ZIKV affects human astrocytes and demonstrate that 1) ZIKV infection reduces cell viability, increases the production of Reactive Oxygen Species (ROS), and results in high viral titers; 2) there are changes in the expression of genes that facilitate the entry of the virus into the cells; 3) there are changes in the expression of genes involved in the homeostasis of the glutamatergic system; and 4) there are ultrastructural changes in mitochondria and lipid droplets associated with production of virions. Our findings reveal new evidence of how ZIKV compromises astrocytic functionality, which may help understand the pathophysiology of ZIKV-associated congenital disease.

Exosomes: from biology to immunotherapy in infectious diseases.

Exosomes are extracellular vesicles derived from the endosomal compartment, which are released by all kinds of eukaryotic and prokaryotic organisms. These vesicles contain a variety of biomolecules that differ both in quantity and type depending on the origin and cellular state. Exosomes are internalized by recipient cells, delivering their content and thus contributing to cell-cell communication in health and disease. During infections exosomes may exert a dual role, on one hand, they can transmit pathogen-related molecules mediating further infection and damage, and on the other hand, they can protect the host by activating the immune response and reducing pathogen spread. Selective packaging of pathogenic components may mediate these effects. Recently, quantitative analysis of samples by omics technologies has allowed a deep characterization of the proteins, lipids, RNA, and metabolite cargoes of exosomes. Knowledge about the content of these vesicles may facilitate their therapeutic application. Furthermore, as exosomes have been detected in almost all biological fluids, pathogenic or host-derived components can be identified in liquid biopsies, making them suitable for diagnosis and prognosis. This review attempts to organize the recent findings on exosome composition and function during viral, bacterial, fungal, and protozoan infections, and their contribution to host defense or to pathogen spread. Moreover, we summarize the current perspectives and future directions regarding the potential application of exosomes for prophylactic and therapeutic purposes.

Prevalence of anti-SARS-CoV-2 antibodies and associated factors in healthcare workers of a Mexican Covid-19 hospital

OBJECTIVE: To determine the prevalence of SARS-CoV-2 antibodies among healthcare workers (HCW) and to identify factors associated with infection. Materials and meth-ods. A cross-sectional study was conducted in a Covid-19 hospital in Morelos, Mexico. Antibodies against SARS-CoV-2 spike and nucleocapsid proteins were detected by ELISA. A bivariate and multivariable Poisson regression model were performed to identify factors associated with infection. RESULTS: Among all participants, 31% had anti-SARS-CoV-2 antibodies, while only 13.1% had reported a history of positive RT-PCR. Individuals who reported cohabiting with someone with Covid-19, and those who had a previous RT-PCR test, were more likely to be seropositive. Laboratory personnel had the lowest seroprevalence (12.0%), while social workers had the highest (35.7%). CONCLUSIONS: The results of this study show the seroprevalence of SARS-CoV-2 antibodies among HCW in a hospital in Mexico, and underline the importance of serological tests for a better estimate of prevalence in health systems where only symptomatic cases are recorded.

IL-34 and protein-tyrosine phosphatase receptor type-zeta-dependent mechanisms limit arthritis in mice.

Myeloid cell mediated mechanisms regulate synovial joint inflammation. IL-34, a macrophage (Mø) growth and differentiation molecule, is markedly expressed in neutrophil and Mø-rich arthritic synovium. IL-34 engages a newly identified independent receptor, protein-tyrosine phosphatase, receptor-type, zeta (PTPRZ), that we find is expressed by Mø. As IL-34 is prominent in rheumatoid arthritis, we probed for the IL-34 and PTPRZ-dependent myeloid cell mediated mechanisms central to arthritis using genetic deficient mice in K/BxN serum-transfer arthritis. Unanticipatedly, we now report that IL-34 and PTPRZ limited arthritis as intra-synovial pathology and bone erosion were more severe in IL-34 and PTPRZ KO mice during induced arthritis. We found that IL-34 and PTPRZ: (i) were elevated, bind, and induce downstream signaling within the synovium in arthritic mice and (ii) were upregulated in the serum and track with disease activity in rheumatoid arthritis patients. Mechanistically, IL-34 and PTPRZ skewed Mø toward a reparative phenotype, and enhanced Mø clearance of apoptotic neutrophils, thereby decreasing neutrophil recruitment and intra-synovial neutrophil extracellular traps. With fewer neutrophils and neutrophil extracellular traps in the synovium, destructive inflammation was restricted, and joint pathology and bone erosion diminished. These novel findings suggest that IL-34 and PTPRZ-dependent mechanisms in the inflamed synovium limit, rather than promote, inflammatory arthritis.