抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Immunological dysregulation is the cause of many non-infectious human diseases such as autoimmunity, allergy and cancer. The gastrointestinal tract is the primary site of interaction between the host immune system and microorganisms, both symbiotic and pathogenic. In this Review we discuss findings indicating that developmental aspects of the adaptive immune system are influenced by bacterial colonization of the gut. We also highlight the molecular pathways that mediate host–symbiont interactions that regulate proper immune function. Finally, we present recent evidence to support that disturbances in the bacterial microbiota result in dysregulation of adaptive immune cells, and this may underlie disorders such as inflammatory bowel disease. This raises the possibility that the mammalian immune system, which seems to be designed to control microorganisms, is in fact controlled by microorganisms.

The gut microbiota shapes intestinal immune responses during health and disease

Authors Jan L. Brozek, MD, PhD – Department of Clinical Epidemiology & Biostatistics and Medicine, McMaster University, Hamilton, Canada Jean Bousquet, MD, PhD – Service des Maladies Respiratoires, Hopital Arnaud de Villeneuve, Montpellier, France, INSERM, CESP U1018, Respiratory and Environmental Epidemiology Team, France, and WHO Collaborating Center for Rhinitis and Asthma Carlos E. Baena-Cagnani, MD – Faculty of Medicine, Catholic University of Cordoba, Cordoba, Argentina Sergio Bonini, MD – Institute of Neurobiology and Molecular Medicine – CNR, Rome, Italy and Department of Medicine, Second University of Naples, Naples, Italy G. Walter Canonica, MD – Allergy & Respiratory Diseases, DIMI, Department of Internal Medicine, University of Genoa, Genoa, Italy Thomas B. Casale, MD – Division of Allergy and Immunology, Department of Medicine, Creighton University, Omaha, Nebraska, USA Roy Gerth van Wijk, MD, PhD – Section of Allergology, Department of Internal Medicine, Erasmus Medical Centre, Rotterdam, the Netherlands Ken Ohta, MD, PhD – Division of Respiratory Medicine and Allergology, Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan Torsten Zuberbier, MD – Department of Dermatology and Allergy, Charite Universitatsmedizin Berlin, Berlin, Germany Holger J. Schunemann, MD, PhD, MSc – Department of Clinical Epidemiology & Biostatistics and Medicine, McMaster University, Hamilton, Canada

/pdf/allergic-rhinitis-and-its-impact-on-asthma-20b4c7y0pr.pdf

Allergic Rhinitis and Its Impact on Asthma

http://www.umassmed.edu/globalassets/immunology-and-microbiology/documents/papers-for-bbs821-2015/nov-24-reviewfor-general-info.pdf

Role of the Microbiota in Immunity and Inflammation

CD4+ T regulatory cells (Tregs), which express the Foxp3 transcription factor, play a critical role in the maintenance of immune homeostasis. Here, we show that in mice, Tregs were most abundant in the colonic mucosa. The spore-forming component of indigenous intestinal microbiota, particularly clusters IV and XIVa of the genus Clostridium, promoted Treg cell accumulation. Colonization of mice by a defined mix of Clostridium strains provided an environment rich in transforming growth factor–β and affected Foxp3+ Treg number and function in the colon. Oral inoculation of Clostridium during the early life of conventionally reared mice resulted in resistance to colitis and systemic immunoglobulin E responses in adult mice, suggesting a new therapeutic approach to autoimmunity and allergy.

/pdf/induction-of-colonic-regulatory-t-cells-by-indigenous-3lbzi76jax.pdf

Induction of Colonic Regulatory T Cells by Indigenous Clostridium Species

Vagus nerve stimulation effective in treating mood disorders include application of bursts of vagus nerve stimulation pulses having an average inter-burst duration and an average inter-pulse duration within selected intervals. The effectiveness of test agents in treating mood disorders can be determined by monitoring the firing pattern induced by the test agents on the vagus nerve. Test agents capable of inducing a firing pattern of vagus nerve pulses with average inter-burst duration and average inter-pulse duration within the selected intervals are identified as useful in treating a mood disorder.

Vagus nerve stimulation and monitoring

Immune to fear: With a little help from old friends.

We thank McLean and colleagues (1) for their comments on our recent study (2). They make two major points. First, they point out that there are differences between the functional effects obtained by them with their Bifidobacteria and those obtained by us with our Lactobacillus strain. To us, this is hardly surprising, and we categorically stated in the Discussion of our paper “Moreover, probiotic effects are strain dependent” (ref. 2, p. 16054). Indeed, it is perfectly conceivable and even likely in our opinion that the effects of probiotics on brain function can occur through different mechanisms, both humoral and neural. Many potential probiotics have been shown to have immune-modulating activity (3) and it is long established that dysregulation in the immune system can bidirectionally affect the brain in a manner relevant to mood and anxiety disorders (4). Second, they argue that models based on infection or colitis may be superior for assessing anxiety-like behavior. We agree that there may be some justification in this position if we were primarily focused on anxiety-like behavior associated with or after infection and inflammation, but the scope of our study was broader and encompassed all aspects of anxiety- and stress-related disorders outside of that aspect comorbid with gastrointestinal disorders. This is the reason we feel our study was an advance on previous exciting research from McLean et al. and others using infection-based models. Heuristically, the fact that modulation of the gut microbiota reverses behavioral effects in an animal model of gastrointestinal dysfunction is perhaps not as surprising as our data (2) that acted as a proof of principle that a potential probiotic bacterium affects a multitude of functional readouts across the brain–gut–microbiome axis under normal physiological conditions or exposure to an acute stressor.

https://www.pnas.org/content/pnas/109/4/E176.full.pdf

Reply to McLean et al. and Burnet: The microbiome-gut-brain axis as a pathway toward next generation psychotropics

Background Cough is a common troublesome symptom in asthma which is neuronally mediated. Limosilactobacillus reuteri DSM-17938 (L. reuteri DSM-17938) is a probiotic shown to be effective in pre-clinical models at suppressing neuronal responses to capsaicin, a transient receptor potential vanilloid agonist (TRPV1). Objective Investigate the effects of DSM-17938 versus matched placebo on capsaicin-evoked coughs in mild allergic asthmatics. Methods We performed a 4-visit, randomized, double-blind, placebo-controlled, two-way cross-over study comparing full dose cough responses with inhaled capsaicin in mild allergic asthmatics after 1 month of treatment with DSM-17938 compared with matched placebo. Randomization and allocation to trial group were carried out by a central computer system. Histamine skin prick testing, airway hyper-responsiveness and inflammatory cells in induced sputum were measured at every visit. Blood was collected to extract PBMCs and stimulated with CD3/CD28 to ascertain the effects of DSM-17938 /placebo on T-cell cytokine responses. Results Seventeen subjects were recruited and 15 completed the study (8 females, mean age 27.3 years). There was no difference in the change in maximum capsaicin-evoked coughs (Emax) after treatment with L. reuteri DSM-17938 compared with placebo [mean difference 2.07 coughs (95% CI -2.77 to 6.91, p = .38) or relative changes in geometric mean ratios for the dose evoking at least half the Emax (ED50) [1.05 (95% CI 0.31-3.58, p = .94)], concentration evoking 2 coughs (C2) [0.63 (0.26-1.53), p = .28] and 5 coughs (C5) [0.79 (0.25-2.50), p = .67]. There was no effect on histamine skin prick wheal size, intensity of itch sensation, methacholine PC20, airway inflammation or T-cell responses after stimulation with CD3/CD28. There were no serious adverse events. One subject developed a mild upper respiratory tract infection and another mild transient nausea whilst on DSM-17938. Conclusion In this small study in adults with mild allergic asthma, we found no evidence that L. reuteri DSM-17938 has any systemic effects on airway nerves, smooth muscle, sputum inflammatory cells, skin responses or T-cell responses after oral consumption. Trial registration Clinicaltrials.gov Identifier: NCT03603522.

Limosilactobacillus reuteri DSM-17938 for preventing cough in adults with mild allergic asthma: A double-blind randomized placebo-controlled cross-over study.

Paul Forsythe

Papers

Vagus nerve stimulation and monitoring

Immune to fear: With a little help from old friends.

Reply to McLean et al. and Burnet: The microbiome-gut-brain axis as a pathway toward next generation psychotropics

Limosilactobacillus reuteri DSM-17938 for preventing cough in adults with mild allergic asthma: A double-blind randomized placebo-controlled cross-over study.