A better understanding of all immune components involved in protecting against Mycobacterium tuberculosis infection is urgently needed to inform strategies for novel immunotherapy and tuberculosis (TB) vaccine development. Although cell-mediated immunity is critical, increasing evidence supports that antibodies also have a protective role against TB. Yet knowledge of protective antigens is limited. Analyzing sera from 97 US immigrants at various stages of M. tuberculosis infection, we showed protective in vitro and in vivo efficacy of polyclonal IgG against the M. tuberculosis capsular polysaccharide arabinomannan (AM). Using recently developed glycan arrays, we established that anti-AM IgG induced in natural infection is highly heterogeneous in its binding specificity and differs in both its reactivity to oligosaccharide motifs within AM and its functions in bacillus Calmette-Guérin vaccination and/or in controlled (latent) versus uncontrolled (TB) M. tuberculosis infection. We showed that anti-AM IgG from asymptomatic but not from diseased individuals was protective and provided data suggesting a potential role of IgG2 and specific AM oligosaccharides. Filling a gap in the current knowledge of protective antigens in humans, our data support the key role of the M. tuberculosis surface glycan AM and suggest the importance of targeting specific glycan epitopes within AM in antibody-mediated immunity against TB.

A better understanding of the epitopes most relevant for antibody-mediated protection against tuberculosis (TB) remains a major knowledge gap. We have shown that human polyclonal IgG against the Mycobacterium tuberculosis ( M . tuberculosis ) surface glycan arabinomannan (AM) and related lipoarabinomannan (LAM) is protective against TB. To investigate the impact of AM epitope recognition and Fcγ receptor (FcγR) binding on antibody functions against M . tuberculosis , we isolated a high-affinity human monoclonal antibody (mAb; P1AM25) against AM and showed its binding to oligosaccharide (OS) motifs we previously found to be associated with in vitro functions of human polyclonal anti-AM IgG. Human IgG1 P1AM25, but not 2 other high-affinity human IgG1 anti-AM mAbs reactive with different AM OS motifs, enhanced M . tuberculosis phagocytosis by macrophages and reduced intracellular growth in an FcγR-dependent manner. P1AM25 in murine IgG2a, but neither murine IgG1 nor a non–FcγR-binding IgG, given intraperitoneally prior to and after aerosolized M . tuberculosis infection, was protective in C57BL/6 mice. Moreover, we demonstrated the protective efficacy of human IgG1 P1AM25 in passive transfer with M . tuberculosis –infected FcγR-humanized mice. These data enhance our knowledge of the important interplay between both antibody epitope specificity and Fc effector functions in the defense against M . tuberculosis and could inform development of vaccines against TB.

Escherichia coli O157: H7 (EHEC) is a major foodborne pathogen largely transmitted to humans through the consumption of undercooked ground beef. This study investigated the efficacy of two food-grade, plant-derived antimicrobials, namely rutin (RT), and resveratrol (RV) with or without chitosan (CH) in enhancing EHEC inactivation in undercooked hamburger patties. Further, the effect of aforementioned treatments on beef color and lipid oxidation was analyzed. Additionally, the deleterious effects of these antimicrobial treatments on EHEC was determined using scanning electron microscopy (SEM). Ground beef was inoculated with a five-strain mixture of EHEC (7.0 log CFU/g), followed by the addition of RT (0.05%, 0.1% w/w) or RV (0.1, 0.2% w/w) with or without CH (0.01% w/w). The meat was formed into patties (25 g) and stored at 4°C for 5 days. On days 1, 3 and 5, the patties were cooked (65°C, medium rare) and surviving EHEC was enumerated. The effect of these treatments on meat color and lipid oxidation during storage was also determined as per American Meat Science Association guidelines. The study was repeated three times with duplicate samples of each treatment. Both RT and RV enhanced the thermal destruction of EHEC, and reduced the pathogen load by at least 3 log CFU/g compared to control (P 0.05). Moreover, patties treated with RV plus chitosan were more color stable with higher a* values (P < 0.05). SEM results revealed that heat treatment with antimicrobials (CH+RV 0.2%) caused a complete destruction of EHEC cells with pore formation and extrusion of intracellular contents. Results suggest that the aforementioned antimicrobials could be used for enhancing the thermal inactivation of EHEC in undercooked patties; however, detailed sensory studies are warranted.

Dendritic cells (DC) are highly efficient antigen-presenting cells. DC may be used to create DC vaccines against cancer, but the optimal strategies remain to be elucidated. This study aimed to examine the benefits and adverse effects of using esophageal cancer cell antigens to stimulate DC to trigger the specific immune response in patients with esophageal cancer undergoing radiotherapy. This was an observational cohort study performed at Lianshui County People’s Hospital between September 2010 and June 2012. Forty patients with esophageal cancer planned to receive radiotherapy were selected, and 28 received the DC vaccine. DC were isolated, loaded with antigens, and intradermally injected after being cultured for 1 week. One week after injection, the patients underwent a delayed-type hypersensitivity test. Serum Th1 cytokines [interleukin (IL)-2, IL-12, and interferon (IFN)-γ] and antigen-specific IFN-γ⁺CD8⁺ T cells were tested before and after vaccination. Patients were followed up for 2 years. Adverse events were monitored. Patients in the vaccine group tolerated the DC vaccine. Levels of serum IL-2 (+92.4%), IL-12 (+70.9%), and IFN-γ (+214.3%) as well as the proportion of IFN-γ⁺CD8⁺ T cells (3.0–16.4-fold) were significantly increased compared with baseline and the control group (all P<0.05). The 1- (82.1% vs. 50.0%, P=0.04) and 2-year survival (67.8% vs. 33.3%, P=0.04) was improved by vaccination. Only 2 patients showed mild fever. In conclusion, the DC vaccine triggered the specific immune response and induced the secretion of Th1 cytokines. The vaccine may lead to better survival, but this have to be confirmed. Adverse events were rare and mild.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infectious disease caused by SFTS virus, and the number of SFTS cases increased year by year in China. Previous studies had indicated that gut microbiome closely associated with human health and diseases, including infection diseases, liver diseases, gastrointestinal diseases and metabolic diseases. The aim of this study is to investigate the alterations and involvements of gut microbial in SFTS patients. We compared the gut microbiome of 26 SFTS patients between 20 health controls using the Illumina MiSeq sequencing platform. Reduced gut microbiota diversity and dramatic shifts of fecal microbial composition in SFTS patients were observed compared with health controls. In the intestinal microbial of SFTS patients, the Lachnospiraceae and Ruminococcaceae which could produce short-chain fatty acids were clearly dropped compared with health people, meanwhile, Sutterella which have anti-inflammation properties were reduced too. On the contrary, some common opportunistic pathogens like Enterococcus and Streptococcus and endotoxin-producing bacteria Escherichia which could rise the risk of infections were increased in SFTS patients than healthy people, in addition lactate-producing bacteria Lactobacillaceae also significantly increased in SFTS patients. In addition, research findings on the correlation between gut microbiota and biochemical data found that the changes of gut microbiota of SFTS patients were closely associated with clinical symptoms, key serum enzymes, infection and mortality. These alterations of gut microbiome in SFTS patients suggest the potential contributions of gut microbial to the pathogenesis of SFTS.

Objective We investigated the prevalence of restless legs syndrome (RLS) in Japanese patients with type 2 diabetes and assessed the efficacy of pramipexole therapy. Design One hundred patients with type 2 diabetes without secondary causes of RLS were sequentially screened for the 12-week, prospective, single arm study. RLS was screened by essential diagnostic criteria developed by the International Restless Legs Study Group. Diabetic neuropathy was diagnosed by nerve conductance study. Severity of RLS and sleep quality were assessed by the International Restless Legs Rating Scale (IRLS) and the Japanese version of the Pittsburgh Sleep Quality Index (PSQI-J), respectively. Pramipexole was administered for 12 weeks. The primary end point was change in the IRLS score in 12 weeks and secondary end points were change in PSQI-J and glycated haemoglobin (HbA1c) in 12 weeks. Results RLS was diagnosed in 8 of 100 participants (8%). Diabetic neuropathy was most likely associated with RLS (OR 3.81, 95% CI 0.85 to 17.05, p=0.111). The IRLS score was improved from 19.0±5.6 to 5.4±4.8 by pramipexole in 12 weeks (p<0.001). The change in the score was −13.6 (95% CI −15.5 to −11.7; p<0.05). PSQI-J was improved from 6.0±4.4 to 1.5±1.3 in 12 weeks (p<0.05). Change in PSQI-J was −4.5 (95% CI −6.8 to −2.1; p<0.05). HbA1c was slightly decreased from 7.19±0.56% (55±6 mmol/mol) to 6.90±0.48% (52±5 mmol/mol) in 12 weeks (p<0.05). Change in HbA1c was −0.29% (−3 mmol/mol) (95% CI −0.37% to −0.20% (−4 to −2 mmol/mol;) p<0.05). Conclusions We find that type 2 diabetes is a possible risk factor for RLS in the Japanese population, and that pramipexole treatment can improve the symptoms of RLS as well as the quality of sleep and glycaemic control in these patients. Trial registration number University hospital Medical Information Network in Japan (UMIN000008347).