Regulatory T Cell in Stroke: A New Paradigm for Immune Regulation

Stroke is a common, debilitating trauma that has an incompletely elucidated pathophysiology and lacks an effective therapy. FoxP3+CD25+CD4+ regulatory T cells (Tregs) suppress a variety of normal physiological and pathological immune responses via several pathways, such as inhibitory cytokine secretion, direct cytolysis induction, and antigen-presenting cell functional modulation. FoxP3+CD25+CD4+ Tregs are involved in a variety of central nervous system diseases and injuries, including axonal injury, neurodegenerative diseases, and stroke. Specifically, FoxP3+CD25+CD4+ Tregs exert neuroprotective effects in acute experimental stroke models. These beneficial effects, however, are difficult to elucidate. In this review, we summarized evidence of FoxP3+CD25+CD4+ Tregs as potentially important immunomodulators in stroke pathogenesis and highlight further investigations for possible immunotherapeutic strategies by modulating the quantity and/or functional effects of FoxP3+CD25+CD4+ Tregs in stroke patients

Magnetosome Gene Duplication as an Important Driver in the Evolution of Magnetotaxis in the Alphaproteobacteria

The evolution of microbial magnetoreception (or magnetotaxis) is of great interest in the fields of microbiology, evolutionary biology, biophysics, geomicrobiology, and geochemistry. Current genomic data from magnetotactic bacteria (MTB), the only prokaryotes known to be capable of sensing the Earth’s geomagnetic field, suggests an ancient origin of magnetotaxis in the domain Bacteria. Vertical inheritance, followed by multiple independent magnetosome gene cluster loss, is considered to be one of the major forces that drove the evolution of magnetotaxis at or above the class or phylum level, although the evolutionary trajectories at lower taxonomic ranks (e.g., within the class level) remain largely unstudied. Here we report the isolation, cultivation, and sequencing of a novel magnetotactic spirillum belonging to the genus Terasakiella (Terasakiella sp. strain SH-1) within the class Alphaproteobacteria. The complete genome sequence of Terasakiella sp. strain SH-1 revealed an unexpected duplication event of magnetosome genes within the mamAB operon, a group of genes essential for magnetosome biomineralization and magnetotaxis. Intriguingly, further comparative genomic analysis suggests that the duplication of mamAB genes is a common feature in the genomes of alphaproteobacterial MTB. Taken together, with the additional finding that gene duplication appears to have also occurred in some magnetotactic members of the Deltaproteobacteria, our results indicate that gene duplication plays an important role in the evolution of magnetotaxis in the Alphaproteobacteria and perhaps the domain Bacteria

Acquired tonsillar herniation related to spontaneous intracranial hypotension: case reports

BackgroundAcquired prolapse of the cerebellar tonsils in spontaneous intracranial hypotension (SIH) patients is rare. This study aims to evaluate neuroimaging changes of acquired prolapse of the cerebellar tonsils below the foramen magnum in SIH patients due to spontaneous spinal cerebrospinal fluid leakage, which was treated by targeted epidural blood patches (EBP).MethodsWe retrospectively reviewed clinical and neuroimaging characteristics of 5 cases of SIH with acquired prolapse of the cerebellar tonsils that received targeted EBP in our institution from January 2013 to December 2016.ResultsOf these SIH patients, all of them suffered from an orthostatic headache. Initial cranial MRI demonstrated descent of the cerebellar tonsils ≥5 mm. Intrathecal gadolinium-enhanced spinal MR myelography and/or spinal MR hydrography were performed to evaluate the level of spinal cerebrospinal fluid leakage. Symptoms were alleviated in all 5 patients after two (n = 4), or three (n = 1) targeted EBP during hospitalization. Follow-up cranial MRI revealed that the descent of cerebellar tonsils was reversed after EBP treatment.ConclusionAcquired tonsillar herniation can occur in patients with SIH and spinal cerebrospinal fluid leakage. Symptoms of these patients may be resolved and radiologic findings may be reversed after EBP treatment

Toll-like receptor 5-mediated IL-17C expression in intestinal epithelial cells enhances epithelial host defense against F4+ ETEC infection

International audienceAbstractEnterotoxigenic Escherichia coli (ETEC) are an important cause of post-weaning diarrhea (PWD) in piglets. The IL-17 cytokine family is well known to play important roles in the host defense against bacterial infections at the mucosa. Previously, we reported the potential role of IL-17A in clearing an ETEC infection in piglets. IL-17C, another member of the IL-17 family, is highly expressed in the intestinal epithelium, however, its role during an ETEC infection is still unclear. In this study, we demonstrate that F4+ ETEC induce IL-17C mRNA and protein expression in intestinal tissues as well as in porcine intestinal epithelial cells (IPEC-J2). This IL-17C production is largely dependent on TLR5 signaling in IPEC-J2 cells. Both F4+ ETEC infection and exogenous IL-17C increased the expression of antimicrobial peptides and tight junction proteins, such as porcine beta-defensin (pBD)-2, claudin-1, claudin-2 and occludin in IPEC-J2 cells. Taken together, our data demonstrate that TLR5-mediated IL-17C expression in intestinal epithelial cells enhances mucosal host defense responses in a unique autocrine/paracrine manner in the intestinal epithelium against ETEC infection

Protective Effect Against Toxoplasmosis in BALB/c Mice Vaccinated With Toxoplasma gondii Macrophage Migration Inhibitory Factor

Toxoplasma gondii is an obligate intracellular parasite responsible for toxoplasmosis, which can cause severe disease in the fetus and immunocompromised individuals. Developing an effective vaccine is crucial to control this disease. Macrophage migration inhibitory factor (MIF) has gained substantial attention as a pivotal upstream cytokine to mediate innate and adaptive immune responses. Homologs of MIF have been discovered in many parasitic species, and one homolog of MIF has been isolated from the parasite Toxoplasma gondii. In this study, the recombinant Toxoplasma gondii MIF (rTgMIF) as a protein vaccine was expressed and evaluated by intramuscular injection in BALB/c mice. We divided the mice into different dose groups of vaccines, and all immunizations with purified rTgMIF protein were performed at 0, 2, and 4 weeks. The protective efficacy of vaccination was analyzed by antibody assays, cytokine measurements and lymphoproliferative assays, respectively. The results obtained indicated that the rTgMIF vaccine elicited strong humoral and cellular immune responses with high levels of IgG antibody and IFN-γ production compared to those of the controls, in addition to slight higher levels of IL-4 production. After vaccination, a stronger lymphoproliferative response was also noted. Additionally, the survival time of mice immunized with rTgMIF was longer than that of the mice in control groups after challenge infection with virulent T. gondii RH tachyzoites. Moreover, the number of brain tissue cysts in vaccinated mice was reduced by 62.26% compared with the control group. These findings demonstrated that recombinant TgMIF protein is a potential candidate for vaccine development against toxoplasmosis